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Asrul Akmal Shafie, Yen Wei Lim, Gin Nie Chua, Mohammed Azmi Ahmad Hassali Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Sciences, Universiti Sains, Penang, Malaysia Introduction: The incremental cost-effectiveness ratio (ICER) is typically compared with a reference value to support the cost-effectiveness of a decision. One method for estimating this value is to estimate the willingness-to-pay (WTP) for a quality-adjusted life-year (QALY). This study was conducted to explore the WTP for a QALY in the Malaysian population. Methods: A cross-sectional, contingent valuation study was conducted in Penang, Malaysia. Respondents were selected from randomly chosen geographical grids of Penang. Respondents’ sociodemographic information, qualities of life, and WTP for one additional QALY were collected using predesigned questionnaires in face-to-face interviews. WTP values were elicited using a double-bound dichotomous choice via a bidding game approach. The Heckman selection model was applied to the analysis of the mean WTP/QALY values, where the “protest zero” values, which may contribute to selection bias, were excluded. Results: The mean value of WTP for an additional QALY gained was estimated to be MYR (Malaysian Ringgit) 29,080 (~USD 9,000). Key factors that affected the WTP include ethnicity and estimated monthly household income. Conclusion: The study findings suggested that the cost-effectiveness threshold value as studied in Penang, Malaysia was estimated to be MYR 29,080. Keywords: WTP, QALY, cost-effectiveness threshold, contingent valuation method, Malaysia

BACKGROUND: Insertional Achilles tendinopathy may be associated with Haglund’s deformity and result in chronic pain. It is usually refractory to conservative management. The aim of this study was to assess the outcome of calcaneoplasty performed in our hospital. METHODS: Eight patients were prospectively evaluated pre- and postoperatively using the American Orthopaedic Foot and Ankle Society (AOFAS) Hindfoot Score, Visual Analogue Scale (VAS) and Short Form (SF) 36, as well as satisfaction rate. Average follow-up duration was 12.4 months. Results: The mean pre and post-operative AOFAS scores were significantly improved at three and six months. SF 36 improved in most parameters. The postoperative VAS score improved significantly and was 0 at 2 years. The procedure was rated as good to excellent by seven of the subjects. Conclusion: We recommend calcaneoplasty for the treatment of insertional Achilles tendinopathy.

Purpose: There is no global definition of well-being. Cultural differences in the perception of well-being and the social and behavioral contexts further limit its measurement. Existing instruments are developed in Western societies that differ in their conceptualization of well-being from Asian populations. Moreover, very few instruments address the multidimensional construct of well-being.Methods: Literature was reviewed to develop a priori conceptual framework of mental health and well-being. Concepts were identified based on specific criteria to guide the qualitative investigations. Finally, focus group discussions were conducted among adults belonging to the three major ethnicities in Singapore to identify salient domains of mental health and well-being.Results: Mental well-being is a multidimensional construct constituting of positive affect, satisfaction, and psychological functioning. While well-being explains the functional and psychological components, positive mental health is a combination of these and the skills required to achieve them. Although there is an overlap between the concepts identified from the literature and those identified in Singapore, certain differences existed, particularly with the relevance attributed to family interactions and religiosity or spirituality. Similar findings were observed across the three ethnic groups.Conclusion: Domains identified can be used to develop a culturally relevant instrument in Singapore. [ABSTRACT FROM AUTHOR]

Microarc oxidation (MAO) is a surface treatment that provides nanoporous pits, and thick oxide layers, and incorporates calcium and phosphorus into the coating layer of titanium alloy. We presumed such modification on the surface of titanium alloy by MAO would improve the ability of cementless stems to osseointegrate. We therefore compared the in vitro ability of cells to adhere to MAOed titanium alloy to that of two different types of surface modifications: machined and grit-blasted. We performed energy-dispersive x-ray spectroscopy and scanned electron microscopy investigations to assess the structure and morphology of the surfaces. Biologic and morphologic responses to osteoblast cell lines (SaOS-2) were then examined by measuring cell proliferation, cell differentiation (alkaline phosphatase activity), and alpha v beta 3 integrin. The cell proliferation rate, alkaline phosphatase activity, and cell adhesion in the MAO group increased in comparison to those in the machined and grit-blasted groups. The osteoblast cell lines of the MAO group were also homogeneously spread on the surface, strongly adhered, and well differentiated when compared to the other groups. This method could be a reasonable option for treating the surfaces of titanium alloy for better osseointegration. [ABSTRACT FROM AUTHOR]

Purpose: To compare the thickness of the retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and choroid in healthy electronic cigarette smokers and non-smokers using spectral domain optical coherence tomography (SD-OCT)., Material and Method: 25 healthy electronic cigarette smokers and 25 age- and gender-matched healthy non-smokers were included in the study. RNFL, GCL, IPL and choroidal thickness were measured by SD-OCT using an automated programme. After normality tests, an independent sample t -test was used to analyse the differences in RNFL, GCL, IPL, and choroidal thickness values between the groups., Results: The mean age of electronic cigarette smokers and non-smokers was 33.68 and 33.64 years, respectively. The mean smoking history was 6.6 years (range 5-8 years). Most of the participants smoked 2-5 ml of e-liquid per day (52%), while 36% smoked more than 5 ml and 12% smoked less than 2 ml per day. The mean intraocular pressure in the electronic cigarette smoker group was 15.0 mmHg, while the non-smoker group was 15.32 mmHg. The mean axial length in the electronic cigarette smoker group and non-smoker group was 23.36 and 23.63 mm, respectively. No significant difference was observed regarding RNFL, GCL, IPL or choroidal thickness between both groups., Conclusion: The thickness of the RNFL, GCL, IPL, and choroid was found to be similar in both the healthy electronic cigarette smokers and non-smokers groups.

Purpose: Scalp cooling therapy (SCT) improves chemotherapy-induced alopecia (CIA), but there are few published data about its efficacy in an Asian-predominant population. We report our tertiary institution experience of SCT in patients with breast or gynaecological cancers undergoing chemotherapy., Methods: The Paxman scalp cooling system was employed for eligible women with breast or gynaecological cancers receiving anthracycline or taxane-based chemotherapy. Only patients with Grade (G) 0-1 alopecia by common terminology criteria for adverse events (CTCAE) version 4.0 were eligible initially, but patients with G2 alopecia were later included in the study. SCT was performed at each chemotherapy cycle, commencing 30 min prior to and continuing up to 90 min after completion of the drug infusion. Patients were assessed at the start and end of each session for hair preservation (defined as G0-2 alopecia) and comfort level of SCT (rated on a 5-point visual scale). The primary end point was success of hair preservation or hair regrowth after completion of all cycles of chemotherapy., Results: Eighty-three patients were enrolled over a period of 18 months from December 2017 to October 2019, with a total of 510 scalp cooling cycles performed. 94.0% (n = 78) of patients reported a comfort score of 3 and above, indicating that the procedure was comfortable, upon a 5-point visual scale. Patients receiving weekly paclitaxel had highest success in hair preservation at 76.7% (23/30 patients), with a lower rate of hair preservation observed for the 3 weekly paclitaxel regimen (50%, 2/4 patients). In contrast, only 1 patient (5.3%, 1/19 patients) who underwent chemotherapy with anthracycline and cyclophosphamide achieved hair preservation., Conclusion: SCT is well tolerated in an Asian-predominant population. Among women with breast or gynaecological cancers receiving taxane and/or anthracycline based chemotherapy, those who underwent SCT were about 50% more likely to achieve hair preservation or hair regrowth, as compared to historical controls., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The worldwide nursing shortage has led to the exploration of using robotics to support care delivery and reduce nurses' workload. In this observational, mixed-method study, we examined the implementation of a robotic nurse assistant (RNA) in a hospital ward to support vital signs measurements, medication, and item delivery. Human-robot interaction was assessed in four domains: usability, social acceptance, user experience, and its societal impact. Patients in a general medicine ward were recruited to participate in a one-time trial with the RNA and a post-trial 75-question survey. Patients' interactions with the RNA were video recorded for analysis including patients' behaviours, facial emotions, and visual attention. Focus group discussions with nurses elicited their perceptions of working with the RNA, areas for improvement, and scalability. Sixty-seven patients aged 21-79 participated in the trial. Eight in 10 patients reported positive interactions with the RNA. When the RNA did not perform to expectations, only 25% of patients attributed fault to the RNA. Video analysis showed patients at ease interacting with the RNA despite some technical problems. Nurses saw potential for the RNA taking over routine tasks. However, they were sceptical of real time savings and were concerned with the RNA's ability to work well with older patients. Patients and nurses suggested greater interactivity between RNA and patients. Future studies should examine potential timesaving and whether time saved translated to nurses performing higher value clinical tasks. The utility of improved RNA's social capability in a hospital setting should be explored as well., (© 2024. The Author(s).)

Background : Recent advancements in hip arthroplasty aim to enhance the stability, longevity, and functionality of femoral implants. However, the distal fitting of femoral stems, often caused by metaphyseal-diaphyseal mismatch, remains a significant issue, particularly in patients with Dorr type A femora. Such mismatches can result in suboptimal implant performance, leading to potential complications. This study focuses on evaluating the anatomical compatibility of five representative single-tapered wedge mid-short stems with the mediolateral (ML) anatomy of the proximal femur in an East Asian population, where these mismatches are often more pronounced. Methods : A total of 742 patients from two hospitals, all of whom underwent unilateral primary total hip arthroplasty, were included in the study. The contralateral proximal femur was confirmed to have normal anatomy in each patient. Hip anteroposterior radiographs were used for measurements, which were standardized in conjunction with CT images. Key anatomical parameters were measured, including proximal and distal medial-lateral canal dimensions, vertical offset, and medial offset. Five femoral stem designs-Tri-lock ® , Taperloc ® , Anthology ® , Accolade II ® , and Fit ® -were evaluated. R programming was employed for a detailed fit analysis to match stem sizes with patient anatomy, categorizing the fit as proximal, simultaneous proximal-distal, or distal engagement. Results : Among the femoral stems analyzed, the Fit ® stem demonstrated the closest alignment with the regression line for ML widths in the study population (slope = 0.69; population ML slope = 0.38). This was followed by Accolade II ® , which had a slope of 0.83. In terms of offset options, the Accolade II ® offered the largest offset coverage, making it particularly suitable for this population. The fit analysis revealed that the Fit ® stem had the highest suitable fit rate (90.56%), followed by Accolade II ® (73.04%). Taperloc ® , Anthology ® , and Tri-lock ® had similar fit rates of approximately 59%. Overall, optimal results were obtained for 92.05% of the population in the automated fitting trial, regardless of the product type. Conclusions : When designing modern cementless femoral stems intended for press-fit fixation, it is crucial to account for the anatomical variations specific to the target population. In this study, Fit ® and Accolade II ® femoral components demonstrated superior compatibility with the femoral anatomy of the East Asian population, particularly in those with a higher incidence of Dorr type A femora. These stems, characterized by slimmer distal dimensions and high-offset options, appear to minimize metaphyseal-diaphyseal mismatch and associated complications.

Objective: Korea's healthcare system and policy promotes early, actively stroke treatment to improve prognosis. This study represents stroke epidemiology and outcomes in Korea., Methods: This study investigated data from the Acute Stroke Assessment Registry. The registry collects data from over 220 hospitals nationwide, focusing on quality stroke service management. Data analysis included patient demographics, stroke severity assessment, and discharge prognosis measurement using standardized scales., Results: 86,568 acute stroke patients were collected with demographic and clinical characteristics during 18 months from 2016 to 2021, focusing on acute subarachnoid hemorrhage, acute intracerebral hemorrhage, and acute ischemic stroke. Of these 86,568 patients, 8.3% was subarachnoid hemorrhage, 16.3% intracerebral hemorrhage, and 74.9% ischemic stroke. Trends showed decreasing subarachnoid hemorrhage and increasing intracerebral hemorrhage cases over the years. 68.3% stroke patients had the clear onset time. 49.6 % stroke patients arrived within 4.5 hours of symptom onset, with more treated at general hospitals. Good functional outcomes at discharge was obtained with 58.3% of acute stroke patients, 55.9% of subarachnoid hemorrhage patients, 34.6% of intracerebral hemorrhage patients, and 63.8% of ischemic stroke patients., Conclusion: The results showed that ischemic stroke was the most common subtype, followed by intracerebral hemorrhage and subarachnoid hemorrhage. Prognosis differed among subtypes, with favorable outcomes more common in ischemic stroke and subarachnoid hemorrhage compared to intracerebral hemorrhage.

Significance: The skin's mechanical properties are tightly regulated. Various pathologies can affect skin stiffness, and understanding these changes is a focus in tissue engineering. Ex vivo skin scaffolds are a robust platform for evaluating the effects of various genetic and molecular interactions on the skin. Transforming growth factor-beta ( TGF - β ) is a critical signaling molecule in the skin that can regulate the amount of collagen and elastin in the skin and, consequently, its mechanical properties., Aim: This study investigates the biomechanical properties of bio-engineered skin scaffolds, focusing on the influence of TGF - β , a signaling molecule with diverse cellular functions., Approach: The TGF - β receptor I inhibitor, galunisertib, was employed to assess the mechanical changes resulting from dysregulation of TGF - β . Skin scaffold samples, grouped into three categories (control, TGF - β -treated, and TGF - β + galunisertib-treated), were prepared in two distinct culture media-one with aprotinin (AP) and another without. Two optical elastography techniques, namely wave-based optical coherence elastography (OCE) and Brillouin microscopy, were utilized to quantify the biomechanical properties of the tissues., Results: Results showed significantly higher wave speed (with AP, p < 0.001 ; without AP, p < 0.001 ) and Brillouin frequency shift (with AP, p < 0.001 ; without AP, p = 0.01 ) in TGF - β -treated group compared with the control group. The difference in wave speed between the control and TGF - β + galunisertib with ( p = 0.10 ) and without AP ( p = 0.36 ) was not significant. Moreover, the TGF - β + galunisertib-treated group exhibited lower wave speed without and with AP and reduced Brillouin frequency shift than the TGF - β -treated group without AP, further strengthening the potential role of TGF - β in regulating the mechanical properties of the samples., Conclusions: These findings offer valuable insights into TGF - β -induced biomechanical alterations in bio-engineered skin scaffolds, highlighting the potential of OCE and Brillouin microscopy in the development of targeted therapies in conditions involving abnormal tissue remodeling and fibrosis., (© 2024 The Authors.)

Objective: Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS)., Methods: We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available., Results: 64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage. Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progression-free survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA , FGFR2 , and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0-16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%., Conclusion: Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted., Competing Interests: Natalie YL Ngoi reports honorarium and travel from AstraZeneca, and honorarium from Pfizer and Merck., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

The genus Fuscoporia ( Hymenochaetaceae , Basidiomycota ) comprises poroid white-rot fungi characterized by dark brown hymenial setae, a dimitic hyphal system, and encrusted generative hyphae. Despite the ecological and commercial significance of Fuscoporia species, their identification has been challenging owing to their morphological overlap with other genera of Hymenochaetaceae and to the limited resolution of nuclear ribosomal DNA markers. With the advances in molecular research, Fuscoporia has been revised to include species from Inonotus sensu lato and Phellinus sensu lato, and 71 new species have been reported over the past decade. In Korea, a comprehensive taxonomic study elucidating the true diversity of Fuscoporia is yet to be conducted. Among the 11 Fuscoporia species reported in Korea, two were identified solely based on morphological characteristics, and four were identified based on nuclear ribosomal DNA regions, which have limited resolution for species identification in Fuscoporia . To investigate the current status of Fuscoporia species native to Korea, we conducted a phylogenetic study using four genetic markers (ITS + nrLSU +  RPB2  +  TEF1 ), along with morphological characteristics, and re-analyzed the GenBank records deposited from Korea. Ten Fuscoporia species were identified, including three previously unrecorded species. A detailed description of the unrecorded species and a list of proposed Korean names for all Fuscoporia species in Korea are provided. This study will guide further taxonomic and applied research of Fuscoporia by providing a species identification key and a verified multigenetic database, in addition to confirming the sequences in public database., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)

Hymenochaetales Oberw. is an order classified in Basidiomycota of Fungi, and species in this order display notable diversity. They exhibit various fruiting body shapes, including clavarioid, effused-reflexed, and resupinate basidiomes. Few mycorrhizal species have been reported in Hymenochaetales, but wood-decaying species dominate the order. Hymenochaetaceae Imazeki & Toki and Schizoporaceae Jülich are the most species-rich families within Hymenochaetales, and most species in the Republic of Korea belong to these two families. As such, current taxonomic classification and nomenclature are not reflected upon species in the remaining Hymenochaetales families. For this study, a multifaceted morphological and multigenetic marker-based phylogenetic investigation was conducted to, firstly, comprehensively identify understudied Hymenochaetales specimens in Korea and, secondly, reflect the updates on the species classification. Five genetic markers were assessed for the phylogenetic analysis: nuclear small subunit ribosomal DNA (nSSU), internal transcribed spacer (ITS), nuclear large subunit ribosomal DNA (nLSU), RNA polymerase II subunit 2 gene (RPB2), and translation elongation factor 1 gene (TEF1). The results from phylogenetic analysis supported 18 species classified under eight families (excluding Hymenochaetaceae and Schizoporaceae) in Korea. Species formerly placed in Rickenellaceae and Trichaptum sensu lato have been systematically revised based on recent taxonomic reconstructions. In addition, our findings revealed one new species, Rickenella umbelliformis, and identified five formerly nationally unreported species classified under five understudied families. Our findings contribute to a better understanding of Hymenochaetales diversity and highlight the need for continued research., (© 2024. The Author(s).)

Background: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications., Materials and Methods: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility., Results: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71)., Conclusions: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Molecular profiling of metastatic breast cancer (MBC) through the widespread use of next-generation sequencing (NGS) has highlighted actionable mutations and driven trials of targeted therapy matched to tumour molecular profiles, with improved outcomes reported using such an approach. Here, we review NGS results and treatment outcomes for a cohort of Asian MBC patients in the phase I unit of a tertiary centre., Methods: Patients with MBC referred to a phase I unit underwent NGS via Ion AmpliSeq Cancer Hotspot v2 (ACH v2, 2014-2017) prior to institutional change to FoundationOne CDx (FM1; 2017-2022). Patients were counselled on findings and enrolled on matched therapeutic trials, where available. Outcomes for all subsequent treatment events were recorded to data cut-off on January 31, 2022., Results: A total of 215 patients were enrolled with successful NGS in 158 patients. The PI3K/AKT/PTEN pathway was the most altered with one or more of the pathway member genes PIK3/AKT/PTEN affected in 62% (98/158) patients and 43% of tumours harbouring a PIK3CA alteration. Tumour mutational burden (TMB) was reported in 96/109 FM1 sequenced patients, with a mean TMB of 5.04 mt/Mb and 13% (12/96) with TMB ≥ 10 mt/Mb. Treatment outcomes were evaluable in 105/158 patients, with a pooled total of 216 treatment events recorded. Matched treatment was administered in 47/216 (22%) events and associated with prolonged median progression-free survival (PFS) of 21.0 weeks [95% confidence interval (CI) 11.7, 26.0 weeks] versus 12.1 weeks (95% CI 10.0, 15.4 weeks) in unmatched, with hazard ratio (HR) for progression or death of 0.63 (95% CI 0.41, 0.97; p = 0.034). In the subgroup of PIK3/AKT/PTEN -altered MBC, the HR for progression or death was 0.57 (95% CI 0.35, 0.92; p = 0.02), favouring matched treatment. Per-patient overall survival (OS) analysis (n = 105) showed improved survival for patients receiving matched treatment versus unmatched, with median OS (mOS) of 30.1 versus 11.8 months, HR = 0.45 (95% CI 0.24, 0.84; p = 0.013). Objective response rate (ORR) in the overall population was similar in matched and unmatched treatment events (23.7% versus 17.2%, odds ratio of response 1.14 95% CI 0.50, 2.62; p = 0.75)., Conclusions: Broad-panel NGS in MBC is feasible, allowing therapeutic matching, which was associated with improvements in PFS and OS., Competing Interests: RW reported serving on the advisory board of Pfizer and Novartis and receiving honoraria from Pfizer, AstraZeneca, Novartis, and Merck MSD and travel funding from Merck MSD outside the submitted work. NN reported honoraria from Merck, MSD, AstraZeneca, and ASGO; research funding from Cyclacel and iOnctura; and travel funding from AstraZeneca and JSGO. SO reported honoraria and consulting with Astra Zeneca, Pfizer, Novartis, Eli Lilly, and Roche. AW reported advisory board membership and/or speaker activity with honoraria with AstraZeneca, Novartis, Eisai, DKSH, Pfizer, and Roache and research funding from Otsuka Pharmaceuticals. VH reported consultancy/advisory activity with DKSH, AstraZeneca, Novartis, MSD, and Pfizer. RS reported serving on the advisory board of Bristol Myers Squibb, Merck, Eisai, Bayer, Taiho, Novartis, MSD, DKSH, and GSK; receiving honoraria from MSD, Eli Lilly, Bristol Myers Squibb, Roche, Taiho, AstraZeneca, Ipsen, and DKSH; and receiving grants from Roche, AstraZeneca, Taiho, Eisai, DKSH, Paxman Coolers, Natera, and MSD outside the submitted work. RAS reported honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Novartis, Pfizer, Roche/Genentech, Takeda, Yuhan, Amgen, Bayer, Merck, Merck Serono, and Puma Biotechnology; consulting or advisory role with AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Pfizer, Roche/Genentech, Taiho Pharmaceutical, Yuhan, Takeda, Amgen, Lilly, Merck, Janssen, Puma Biotechnology, Merck Serono, Bayer, and Thermo Fisher Scientific; and research funding from AstraZeneca and Boehringer Ingelheim. WY reported consulting or advisory role with AbbVie/Genentech, Amgen, Bristol Myers Squibb, Ipsen, Novartis, and AstraZeneca; speakers’ bureau with Lilly, Sanofi/Aventis, Taiho Pharmaceutical, Eisai, Bayer, and MSD Oncology; and travel and accommodation expenses from Pfizer. SCL reports honoraria and consulting activity with AstraZeneca, Pfizer, Novartis, Eli Lilly, Roche, ACT Genomics, and Eisai and research funding from Taihi, Eisai, Pfizer, and ACT Genomics. JL reported advisory activity with AstraZeneca, Novartis, Roche, DKSH, Pfizer, and MSD; receiving honoraria from AstraZeneca, Novartis, Roche, DKSH, MSD, Eisai, and Pierre Fabre; receiving research funding from CTI BioPharma, Daiichi Sankyo, and Synthon Pharmaceuticals; and receiving travel grant from AstraZeneca and MSD outside the submitted work. DT is an employee of the National University Health System Singapore and reports personal fees for advisory board membership from AstraZeneca, Bayer, BioNTech Boehringer Ingelheim, Eisai, Genmab, GSK, MSD, PMV Pharma, and Roche; personal fees as an invited speaker from AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, and Takeda; ownership of stocks/shares of Asian Microbiome Library AMiLi; institutional research grants from AstraZeneca, Bayer, Karyopharm Therapeutics, and Roche; institutional funding as coordinating PI from AstraZeneca, MSD, Eisai, Roche, and Bergen Bio; institutional funding as local PI from Roche, BioNTech, PMV Pharma, GSK, Sutro Pharma, Bayer, Byondis B.V., and Zeria Pharmaceutical Co., Ltd.; a previous non-renumerated role as Chair of the Asia Pacific Gynecologic Oncology Trials Group APGOT; a previous non-renumerated role as the Society President of the Gynecologic Cancer Group Singapore; non-renumerated membership of the Board of Directors of the GCIG; research funding from the National Medical Research Council NMRC Clinician Scientist Award Senior Investigator Grant CSASI21jun-0003, the Pangestu Family Foundation Gynaecological Cancer Research Fund; and product samples from AstraZeneca, Eisai, and MSD non-financial interest for research trials. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Walsh, Ong, Cheo, Low, Jayagopal, Lee, Ngoi, Ow, Wong, Lim, Lim, Heong, Sundar, Soo, Chee, Yong, Goh, Lee, Tan and Lim.)

Purpose: To investigate the diversity of ocular manifestations in patients with positive perinuclear antineutrophil cytoplasmic antibody (p-ANCA)., Methods: The clinical records of five patients exhibiting ocular manifestations and testing positive for serum MPO-ANCA were retrospectively reviewed., Results: Three out of five patients were female. The youngest patient was aged 26, whereas the eldest was 83 years old. 80% ( n  = 4) of them had purely anterior segment involvement, with the commonest manifestation being peripheral ulcerative keratitis and scleritis. Only one patient had posterior segment involvement, specifically posterior ischemic optic neuropathy. Two patients demonstrated unilateral involvement. There was only one patient diagnosed with systemic involvement, presenting as mixed nephrotic and nephritic syndrome, who required a course of intravenous methylprednisolone during the active stage. Three patients required second-line immunosuppressants throughout the course due to frequent relapse., Conclusion: Anterior segment ocular manifestations are not uncommon and can be the initial presentation of p-ANCA-associated vasculitis (AAV). Therefore, its evaluation should be considered in establishing the diagnosis of AAV, a life-threatening disease.

Obesity is associated with an increased risk of cardiovascular disease. Gambi-jung (GBJ), a modified herbal formula of Taeumjowi-tang, induces weight loss in high-fat diet (HFD)-fed obese mice. Meanwhile, concerns have been raised regarding Ephedra sinica Stapf (ES), the primary herb of GBJ, having potential adverse cardiovascular effects. However, there have been no reports on the effects of ES and ephedrine-containing products on obesity-induced cardiac apoptosis. Therefore, to investigated the effect of GBJ and ES on HFD-induced cardiac apoptosis, we utilized Western blot analysis, TUNEL-staining, and histological staining of heart tissues from HFD-fed obese mice. Western blot analysis showed that there were significant changes in the protein levels of anti-apoptotic markers (B-cell lymphoma (BCL) protein 2 (BCL-2), BCL-XL, and X-linked inhibitor of apoptosis protein) and pro-apoptotic markers (Fas, Fas-associated protein with death domain, BCL-2 agonist of cell death, BCL-2 associated X, cytochrome C, and cleaved caspase-9) in the heart of HFD-fed mice. In contrast administration of 250 mg/kg GBJ for 12 weeks significantly reversed the protein levels related to the apoptosis signaling pathway, which was greater than that of ES administration. Furthermore, GBJ-treated mice had markedly decreased number of TUNEL-stained apoptotic cells compared to the HFD group. Moreover, GBJ improved the mitochondrial function by regulating the genes expression of uncoupling protein 2 , peroxisome proliferator-activated receptor-γ coactivator-1α , optic atrophy protein 1 , and fission protein 1 . Notably, hematoxylin and eosin histological staining showed no changes in the heart tissues of GBJ- and ES-treated mice, indicating that long-term administration of GBJ and ES did not exert any adverse effects on the cardiac tissue. The present study lays the foundation to support the efficacy of GBJ in protecting cardiac cell apoptosis induced by HFD feeding, as well as to verify the cardiac safety of GBJ administration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

To evaluate the technical feasibility of the alternative snare technique using a 0.018-inch guide wire and 5-French (Fr) catheter for double-J ureteral stent (DJUS) removal. In this retrospective study, 11 DJUS were removed in 9 consecutive patients between July 2023 and October 2023. We evaluated patient characteristics, DJUS characteristics, and procedure characteristics. Out of 11 cases, 8 (72.7%) were successful in removing the DJUS using the alternative snare technique without major complications. The average time between DJUS insertion and removal was 47.4 ± 50.0 days. The most common DJUS size was an 8-Fr, with proximal tips predominantly in the proximal ureter and renal pelvis. The mean procedure time for successful cases was 15.2 ± 16.8 minutes. Three failed cases, attributed to obstructions like debris, were later successfully addressed using the ALN inferior vena cava filter removal kit, forceps, and modified snare technique. The alternative snare technique using a 0.018-inch guidewire and Fr catheter is safe and effective in cases of DJUS removal., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Intracerebral hemorrhage (ICH) accompanies higher mortality rates than other type of stroke. This study aimed to investigate the association between hospital volume and mortality for cases of ICH., Methods: We used nationwide data from 2013 to 2018 to compare high-volume hospitals (≥32 admissions/year) and low-volume hospitals (<32 admissions/year). We tracked patients' survival at 3-month, 1-year, 2-year, and 4-year endpoints. The survival of ICH patients was analyzed at 3-month, 1-year, 2-year, and 4-year endpoints using Kaplan-Meier survival analysis. Multivariable logistic regression analysis and Cox regression analysis were performed to determine predictive factors of poor outcomes at discharge and death., Results: Among 9,086 ICH patients who admitted to hospital during 18-month period, 6,756 (74.4%) and 2,330 (25.6%) patients were admitted to high-volume and low-volume hospitals. The mortality of total ICH patients was 18.25%, 23.87%, 27.88%, and 35.74% at the 3-month, 1-year, 2-year, and 4-year, respectively. In multivariate logistic analysis, high-volume hospitals had lower poor functional outcome at discharge than low-volume hospitals (odds ratio, 0.80; 95% confidence interval, 0.72-0.91; p < 0.001). In the Cox analysis, high-volume hospitals had significantly lower 3-month, 1-year, 2-year, and 4-year mortality than low-volume hospitals (p < 0.05)., Conclusion: The poor outcome at discharge, short- and long-term mortality in ICH patients differed according to hospital volume. High-volume hospitals showed lower rates of mortality for ICH patients, particularly those with severe clinical status.

Purpose: Venous thromboembolism (VTE) is a major complication for hip fracture patients, and may exist preoperatively. This study aimed to examine the prevalence of VTE after immediate screening in hip fracture patients., Materials and Methods: Hip fracture patients with an elevated level of D-dimer underwent screening for VTE using computed tomography (CT) angiography. Anticoagulation treatments were administered preoperatively to patients diagnosed with VTE, followed by administration of additional anticoagulation postoperatively. Medical records were reviewed to identify risk factors for preoperative VTE and determine the prognosis of the patients., Results: Among 524 hip fracture patients, 66 patients (12.6%) were diagnosed with VTE, including 42 patients with deep vein thrombosis (DVT), 17 patients with pulmonary thromboembolism (PTE), and 7 patients with both DVT and PTE. Of the patients with VTE, 68.2% were diagnosed within 24 hours of injury, and 33.3% of these patients had PTE. VTE patients showed a tendency toward being overweight ( P <0.01) and not on anticoagulant medication ( P =0.02) compared to patients without VTE. The risk of VTE was higher for femur shaft fractures (odds ratio [OR] 4.83, 95% confidence interval [CI] 2.18-10.69) and overweight patients (OR 2.12, 95% CI 1.17-3.85), and lower for patients who were previously on anticoagulants (OR 0.36, 95% CI 0.18-0.74). Patients with preoperatively diagnosed VTE were asymptomatic before and after surgery., Conclusion: Clinicians should be aware that VTE may be present within 24 hours of injury, and screening for VTE or prophylactic measures should be considered for high-risk patients.

Purpose: Unlike periprosthetic femoral fractures, periprosthetic acetabular fractures during total hip arthroplasty (THA) have not been evaluated in detail. We prospectively evaluated the incidence, patterns, risk factors, and clinical outcomes of intraoperative periprosthetic acetabular fractures using pre- and postoperative computer tomography (CT)., Methods: In this prospective single-centre study, we evaluated 234 consecutive patients (250 hips) who underwent THA and three-dimensional CT before and after the surgery. We assessed the incidence, pattern of fractures, outcomes for each fracture pattern, reoperation and revision rates, Harris hip score, and visual analog scale (VAS) for pain. Multivariate regression models were used to identify risk factors for periprosthetic acetabular fractures., Results: In total, 43 periprosthetic acetabular fractures (17.2%) were identified via CT. Fractures occurred most frequently at the superolateral wall. Early cup migration occurred in three hips. None of the patients underwent revision surgery for acetabular loosening. Regression modeling showed that rheumatoid arthritis was a significant predictor of periprosthetic acetabular fractures., Conclusions: Periprosthetic acetabular fractures are not infrequent during cementless THA and are more common in patients with rheumatoid arthritis., (© 2023. The Author(s) under exclusive licence to SICOT aisbl.)

Introduction: Caregiver burden is a significant issue in the care of patients with advanced kidney disease. Its assessment is crucial for evaluating the needs of caregivers and for the development of interventions to support them. Several instruments have been developed to measure caregiver burden in these patients. However, the measurement properties of these instruments have not been systematically reviewed., Methods and Analysis: This systematic review will include a comprehensive search of databases including PubMed, CINAHL, Embase, Cochrane Library, SCOPUS and Web of Science by using keywords and MeSH terms to identify relevant studies starting from each database inception to 1 January 2024 and covering papers in English. The search strategy will combine relevant keywords and database-specific subject headings related to the following concepts: (1) caregivers, (2) burden, stress, distress, (3) chronic kidney disease, end-stage kidney disease, dialysis. Reference lists of eligible articles will also be hand searched. We will include quantitative and qualitative studies evaluating measurement properties of instruments assessing caregiver burden in caregivers of adult patients (aged ≥18 years). Data will be extracted from the selected studies and analysed using the COnsensus-based Standards for the selection of health Measurement INstruments checklist as the study quality assessment tool. Subsequently, the van der Vleuten utility index will be used to critique and categorise the instruments. A narrative that synthesises the utility of all instruments will be presented along with recommendations for the selection of instruments depending on specific clinical contexts. This systematic review will provide an overview of the measurement properties of available instruments, including discussion on reliability, validity and responsiveness. Results from the review may give rise to the subsequent development of most appropriate instrument that could be applied to the assessment of caregiver burden in advanced kidney disease., Ethics and Dissemination: Ethics approval is not required as this study will merely synthesise data from published studies. The results will be disseminated through peer-reviewed publications as well as conference presentations., Prospero Registration Number: CRD42023433906., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The co-design of health care enables patient-centredness by partnering patients, clinicians and other stakeholders together to create services., Methods: We conducted a systematic review of co-designed health interventions for people living with multimorbidity and assessed (a) their effectiveness in improving health outcomes, (b) the co-design approaches used and (c) barriers and facilitators to the co-design process with people living with multimorbidity. We searched MEDLINE, EMBASE, CINAHL, Scopus and PsycINFO between 2000 and March 2022. Included experimental studies were quality assessed using the Cochrane risk of bias tool (ROB-2 and ROBINS-I)., Results: We screened 14,376 reports, with 13 reports meeting the eligibility criteria. Two reported health and well-being outcomes: one randomised clinical trial (n = 134) and one controlled cohort (n = 1933). Outcome measures included quality of life, self-efficacy, well-being, anxiety, depression, functional status, healthcare utilisation and mortality. Outcomes favouring the co-design interventions compared to control were minimal, with only 4 of 17 outcomes considered beneficial. Co-design approaches included needs assessment/ideation (12 of 13), prototype (11 of 13), pilot testing (5 of 13) (i.e. focus on usability) and health and well-being evaluations (2 of 13). Common challenges to the co-design process include poor stakeholder interest, passive participation, power imbalances and a lack of representativeness in the design group. Enablers include flexibility in approach, smaller group work, advocating for stakeholders' views and commitment to the process or decisions made., Conclusions: In this systematic review of co-design health interventions, we found that few projects assessed health and well-being outcomes, and the observed health and well-being benefits were minimal. The intensity and variability in the co-design approaches were substantial, and challenges were evident. Co-design aided the design of novel services and interventions for those with multimorbidity, improving their relevance, usability and acceptability. However, the clinical benefits of co-designed interventions for those with multimorbidity are unclear., (© 2024. The Author(s).)

We aimed to evaluate the effects of obesity treatment with behavioral therapy (BT) and cognitive behavioral therapy (CBT) interventions compared with multiple comparators and find effective techniques or combinations of techniques in BT and CBT interventions for weight loss. We systematically searched electronic databases and selected randomized controlled trials using CBT or BT intervention for obesity treatment in overweight adults or adults with obesity without psychological symptoms. Both pairwise meta-analysis and network meta-analysis were performed to comprehensively evaluate the comparative effects between interventions. We classified the techniques used in BT and CBT interventions and compared the treatment effects between techniques. Compared with no treatment as a common comparator, CBT was most effective for weight loss, followed by BT, usual care (UC), and minimal care (MC). CBT was a more effective intervention than BT, but the effect of CBT compared to BT was not remarkable in network estimates. The most used BT techniques were feedback and monitoring, and the most used CBT technique was cognitive restructuring. Our results indicated that CBT and BT are effective interventions for weight loss, and that successful weight loss requires more aggressive interventions such as BT or CBT than MC and UC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria. Across 54 actinobacterial strains, our approach yielded 124 distinct activator-strain combinations which consistently outperform wild type. Our approach expands accessible metabolite space by nearly two-fold and increases selected metabolite yields by up to >200-fold, enabling discovery of Gram-negative bioactivity in tetramic acid analogs. We envision these findings as a gateway towards a more streamlined, accelerated, and scalable strategy to unlock the full potential of Nature's chemical repertoire., (© 2024. The Author(s).)

Aspergillus species play a crucial role in terrestrial environments as degraders and are well known for producing various secondary metabolites. Recently, Aspergillus species have been discovered in marine environments, exhibiting adaptability to high salinity and producing diverse secondary metabolites with valuable properties. However, limited research has focused on their marine diversity, leading to inaccurate species identification. The current study addresses this gap by investigating diverse marine habitats in the Republic of Korea, including sediment, seawater, seaweed, and marine animals. From three coasts of the Korean Peninsula, 472 Aspergillus strains were isolated from the various marine habitats. A total of 41 species were accurately identified using multigenetic markers: internal transcribed spacer, calmodulin, and β-tubulin. The findings underscore the importance of accurate identification and provide a basis for elucidating the functional role of marine-derived Aspergillus species in marine ecosystems., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)

Nigrospora ( Xylariales , Apiosporaceae ) consists of species of terrestrial plant endophytes and pathogens. Nigrospora has also been reported in marine environments such as mangroves, sea fans, and macroalgae. However, limited research has been conducted on Nigrospora associated with macroalgae. Here, we isolated Nigrospora species from three types of algae (brown, green, and red algae) from Korean islands (Chuja, Jeju, and Ulleung) based on phylogenetic analyses of multigenetic markers: the internal transcribed spacers (ITS), beta-tubulin ( BenA ), and translation elongation factor 1 ( TEF1-α ). A total of 17 Nigrospora strains were isolated from macroalgae and identified as nine distinct species. The majority of Nigrospora species (seven) were found on brown algae, followed by red algae (three), and then green algae (two). To our understanding, this study represents the first account of N. cooperae , N. covidalis , N. guilinensis , N. lacticolonia , N. osmanthi , N. pyriformis , and N. rubi occurring in marine environments. Additionally, this study provides the first report of the occurrence of N. cooperae , N. covidalis , N. guilinensis , N. lacticolonia , and N. osmanthi in South Korea. This study will provide valuable insights for future research exploring the functions of fungi in macroalgal communities., Competing Interests: The authors have declared that no competing interests exist., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)

Background: Longitudinal work on the impact of COVID-19 on population mental health and resilience beyond the first year of the pandemic is lacking. We aimed to understand how mental health and resilience evolved during the pandemic (2020) and two years later (2022) in a multi-ethnic Singaporean population. In addition, we assessed what characteristics were associated with mental health and resilience scores., Methods: We surveyed and analysed two balanced panel samples up to four times between 30 th April 2020 and 11 th July 2022. One panel assessed psychological distress (Kessler-10) and well-being (short Warwick Edinburgh Mental Well-being scale) n = 313, and one panel assessed resilience (10-item Connor-Davidson Resilience Scale © ) n = 583. A linear panel regression model with random effects assessed the temporal patterns for psychological distress, well-being, and resilience., Results: Mean psychological distress scores (Kessler-10) were relatively stable over time and were not statistically significantly worse than baseline at any follow-up. Well-being scores improved over time and were significantly better than baseline by the third survey (22 nd Jul-18th Aug 2020) (0.54 p = 0.007, Cohen's d 0.12). Scores had worsened by the last survey (27 th June-11 th July 2022) but were not significantly different from baseline 0.20 p = 0.30. Resilience scores declined over time. Scores at both follow-ups (14th Aug- 4th Sep 2020 and 27 th June-11 th July 2022) were statistically significantly lower than baseline: -1.69 p < 0.001 (Cohen's d 0.25) and -0.96 p = 0.006 (Cohen's d 0.14), respectively., Conclusions: Our study joins a body of work measuring the longitudinal effects of COVID-19 on population mental health and resilience. While, the magnitude of the effect related to resilience decline is small, our findings indicate that particular attention should be given to ongoing population surveillance, with the aim of maintaining good health and well-being., (© 2023. The Author(s).)

Background: Extracorporeal membrane oxygenation (ECMO) patients have a high incidence of acute kidney injury (AKI). Extracorporeal cardiopulmonary resuscitation (ECPR) patients are more likely to develop AKI than ECMO patients because of serious injury during cardiac arrest (CA)., Objectives: This study aims to assess the occurrence and outcomes of AKI in ECPR and ECMO, and to identify specific risk factors and clinical implications of AKI in ECPR., Methods: This is a retrospective observational study from a single tertiary care hospital in Gwangju, Korea. Adults (≥18 years) who received ECMO with cardiac etiology in the emergency and inpatient departments from January 2015 to December 2021 were included. The patients (n = 169) were divided into two groups, ECPR and ECMO without CA, and the occurrence of AKI was investigated. The primary outcome of the study was in-hospital mortality, and the secondary outcomes were six-month cerebral performance category (CPC) and AKI during hospitalization., Results: The incidence of AKI was significantly higher with ECPR (67.5 %) than with ECMO without CA (38.4 %). ECPR was statistically significant for Expire (adjusted OR (aOR) 2.45, 95 % CI 1.28-4.66) and Poor CPC (2.59, 1.32-5.09). AKI was also statistically significant for Expire (6.69, 3.37-13.29) and Poor CPC (5.45, 2.73-10.88). AKI was the determining factor for the outcomes of ECPR (p = 0.01)., Conclusions: ECPR patients are more likely to develop AKI than ECMO without CA patients. In ECPR patients, AKI leads to poor outcomes. Therefore, clinicians should be careful not to develop AKI in ECPR patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Hydnum is a genus of ectomycorrhizal fungi belonging to the Hydnaceae family. It is widely distributed across different regions of the world, including North America, Europe, and Asia; however, some of them showed disjunct distributions. In recent years, with the integration of molecular techniques, the taxonomy and classification of Hydnum have undergone several revisions and advancements. However, these changes have not yet been applied in the Republic of Korea. In this study, we conducted an integrated analysis combining the morphological and molecular analyses of 30 specimens collected over a period of approximately 10 years in the Republic of Korea. For molecular analysis, the sequence data of the internal transcribed spacer (ITS) region, the large subunit of nuclear ribosomal RNA gene (nrLSU), and a portion of translation elongation factor 1-α ( TEF1 ) were employed as molecular markers. Through this study, we identified eight species that had previously not been reported to occur in the Republic of Korea, including one new species, Hydnum paucispinum . A taxonomic key and detailed descriptions of the eight Hydnum species are provided in this study., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)

Triboelectrification mechanism is still not understood, despite centuries of investigations. Here, we propose a model showing that mechanochemistry is key to elucidate triboelectrification fundamental properties. Studying contact between gold and silicate glasses, we observe that the experimental triboelectric output is subject to large variations and polarity inversions. First principles analysis shows that electronic transfer is activated by mechanochemistry and the tribopolarity is determined by the termination exposed to contact, depending on the material composition, which can result in different charging at the macroscale. The electron transfer mechanism is driven by the interface barrier dynamics, regulated by mechanical forces. The model provides a unified framework to explain several experimental observations, including the systematic variations in the triboelectric output and the mixed positive-negative "mosaic" charging patterns, and paves the way to the theoretical prediction of the triboelectric properties.

A "chemical linearization" approach was applied to synthetic peptide macrocycles to enable their de novo sequencing from mixtures using nanoliquid chromatography-tandem mass spectrometry (nLC-MS/MS). This approach─previously applied to individual macrocycles but not to mixtures─involves cleavage of the peptide backbone at a defined position to give a product capable of generating sequence-determining fragment ions. Here, we first established the compatibility of "chemical linearization" by Edman degradation with a prominent macrocycle scaffold based on bis -Cys peptides cross-linked with the m -xylene linker, which are of major significance in therapeutics discovery. Then, using macrocycle libraries of known sequence composition, the ability to recover accurate de novo assignments to linearized products was critically tested using performance metrics unique to mixtures. Significantly, we show that linearized macrocycles can be sequenced with lower recall compared to linear peptides but with similar accuracy, which establishes the potential of using "chemical linearization" with synthetic libraries and selection procedures that yield compound mixtures. Sodiated precursor ions were identified as a significant source of high-scoring but inaccurate assignments, with potential implications for improving automated de novo sequencing more generally.

Plasma membrane rupture can result in catastrophic cell death. The skeletal muscle fiber plasma membrane, the sarcolemma, provides an extreme example of a membrane subject to mechanical stress since these cells specifically evolved to generate contraction and movement. A quantitative model correlating ultrastructural remodeling of surface architecture with tissue changes in vivo is required to understand how membrane domains contribute to the shape changes associated with tissue deformation in whole animals. We and others have shown that loss of caveolae, small invaginations of the plasma membrane particularly prevalent in the muscle sarcolemma, renders the plasma membrane more susceptible to rupture during stretch. 1 , 2 , 3 While it is thought that caveolae are able to flatten and be absorbed into the bulk membrane to buffer local membrane expansion, a direct demonstration of this model in vivo has been unachievable since it would require measurement of caveolae at the nanoscale combined with detailed whole-animal morphometrics under conditions of perturbation. Here, we describe the development and application of the "active trapping model" where embryonic zebrafish are immobilized in a curved state that mimics natural body axis curvature during an escape response. The model is amenable to multiscale, multimodal imaging including high-resolution whole-animal three-dimensional quantitative electron microscopy. Using the active trapping model, we demonstrate the essential role of caveolae in maintaining sarcolemmal integrity and quantify the specific contribution of caveolar-derived membrane to surface expansion. We show that caveolae directly contribute to an increase in plasma membrane surface area under physiologically relevant membrane deformation conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This is a rare study comparing the radiological and functional outcomes of fixation after reduction with in situ fixation group using Femoral Neck System (FNS). The aim of this study was to introduce a simple, innovative, minimally invasive method to reduce valgus-impacted and tilted femoral neck fractures without soft tissue or cartilage injury., Methods: A retrospective comparative analysis of 46 patients between May 2020 and February 2022 was performed. In the control group, 23 patients underwent in situ fixation without reduction. In the study group, another 23 patients were managed by fixation after reduction using a percutaneous pull-out technique with a full threaded Steinmann pin. Caput-collum-diaphysis (CCD) angle, tilt, and femoral neck shortenings were compared between the two groups. In addition, Harris Hip Score (HHS) was evaluated and compared at 1 year after surgery. Basically, independent samples t-test was used to compare radiological and functional results., Results: Patients' initial valgus and tilt angles were not significantly different between the groups (n.s.). However, the CCD and tilt angles measured immediately and at one year postoperatively were significantly different between the groups (p < 0.05). Regarding femoral neck shortening, shortening in the three directions, the x, y, and z vectors, was significantly less in the reduction group immediately postoperatively and at 1 year post-surgery (p < 0.05). The mean HHS at 1 year postoperatively was 79.7 ± 8.4 in the in situ fixation group and 87.9 ± 6.6 in the reduction groups, and there was a significant difference (p < 0.05)., Conclusion: The pull-out method with a threaded Steinmann pin to reduce valgus-impacted and tilted femoral neck fracture is safe and effective for accomplishing anatomical restoration. This may achieve successful bone union and maintain the femoral neck length and original tilt without nearby soft tissue or cartilage injury., (© 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Introduction: Healthcare integration has become prevalent as health systems manage a growing population of older adults with multi-morbid conditions. The integrated general hospital (IGH) is the latest example of how services can be remodelled to achieve greater care integration., Methods: We conducted a mixed-method evaluation to identify factors impacting the implementation and effectiveness of the IGH model. Data were collected through in-depth interviews (n = 15) and focus group discussions (n = 8 groups) with hospital staff, and a staff survey (n = 226)., Results: Staff perceived improvements in clinical practice and better clinical outcomes for patients. The care model empowered nursing and allied health staff through a more collegial team structure. However, staff reported an unequal workload distribution; a third reported burnout; and some observed inconsistencies between leaders' aspirations for IGH and what was happening on the ground. For IGH to sustain, staff's education on the IGH model needs to be improved. Further examination of work processes is recommended to boost staff morale and prevent burnout., Conclusion: Overall, IGH provided better integrated, team-based care. The model challenged traditional team structures and empowered staff to expand their roles and responsibilities. Policymakers could consider the IGH model a successful approach for integrating services across the care continuum., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Interest in edible and medicinal macrofungi is millennial in terms of their uses in health and food products in Central Asia, while interest in inedible and medicinal macrofungi has grown in popularity in recent years. Edible and inedible medicinal basidiomycetes were collected during field surveys from different regions of Uzbekistan. The morphological characters and similarity assessment of rDNA-Internal Transcribed Spacer sequence data were used to measure diversity and habitat associations. A number of 17 species of medicinal macrofungi of ethnomycological and medicinal interest was found associated with 23 species of trees and shrubs belonging to 11 families and 14 genera. Polyporaceae and Hymenochaetaceae were represented by the highest number of species followed by Ganodermataceae , Fomitopsidaceae , Auriculariaceae , Cerrenaceae , Grifolaceae , Phanerochaetaceae , Laetiporaceae , Schizophyllaceae , and Stereaceae . The highest number of medicinal basidiomycete species was reported in the following host genera: Acer , Betula , Celtis , Crataegus , Juglans , Juniperus , Lonicera , Malus , Morus , Platanus , Populus , Prunus , Quercus , and Salix . An updated list of edible and inedible medicinal mushrooms identified in Uzbekistan, their morphological characteristics, and phylogenetic placement are given for the first time. Information is provided on their uses in traditional and modern medicine. Their bioactive compounds and extracts can be applied as medicines, as well as food and cosmetic ingredients.

Most medical implants are made of titanium. When titanium is exposed to air for a long time, hydrocarbons are deposited and the surface becomes hydrophobic. Cell attachment is important for bone ingrowth to occur on the implant surface, and hydrophilicity can enhance this. We examined whether non-thermal atmospheric pressure plasma treatment could increase the hydrophilicity of the titanium surface. Samples coated with four widely used coating types [grit blasting, micro arc oxidation (MAO), titanium plasma spray (TPS), and direct metal fabrication (DMF)] were treated with plasma. Each of the four surface-treated samples was divided into groups with and without plasma treatment. We analysed wettability by surface analysis and evaluation of contact angles, cell proliferation, and adhesion using scanning electron microscopy (SEM), confocal laser scanning microscopy, absorbance tests, and alkaline phosphatase (ALP) activity assay; four different Ti 6 Al 4 V surface types were compared. After plasma treatment, the contact angle was reduced on all surfaces, and the carbon content was reduced on all surfaces based on X-ray photoelectron spectroscopy (XPS) surface analysis. Under confocal laser scanning, the cell layer was thicker on the plasma-treated samples, especially in groups TPS and DMF. Cell proliferation was 41.8%, 17.7%, 54.9%, and 83.8% greater for the plasma- than non-plasma-treated grit blasting, MAO, TPS, and DMF samples, respectively. Hydrophilicity increased significantly under plasma treatment, and biological responsivity was also improved., (© 2023. Springer Nature Limited.)