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Abstract Over the past five decades, a large number of wild animals have been individually identified by various observation systems and/or temporary tracking methods, providing unparalleled insights into their lives over both time and space. However, so far there is no comprehensive record of uniquely individually identified animals nor where their data and metadata are stored, for example photos, physiological and genetic samples, disease screens, information on social relationships. Databases currently do not offer unique identifiers for living, individual wild animals, similar to the permanent ID labelling for deceased museum specimens. To address this problem, we introduce two new concepts: (1) a globally unique animal ID (UAID) available to define uniquely and individually identified animals archived in any database, including metadata archived at the time of publication; and (2) the digital ‘home’ for UAIDs, the Movebank Life History Museum (MoMu), storing and linking metadata, media, communications and other files associated with animals individually identified in the wild. MoMu will ensure that metadata are available for future generations, allowing permanent linkages to information in other databases. MoMu allows researchers to collect and store photos, behavioural records, genome data and/or resightings of UAIDed animals, encompassing information not easily included in structured datasets supported by existing databases. Metadata is uploaded through the Animal Tracker app, the MoMu website, by email from registered users or through an Application Programming Interface (API) from any database. Initially, records can be stored in a temporary folder similar to a field drawer, as naturalists routinely do. Later, researchers and specialists can curate these materials for individual animals, manage the secure sharing of sensitive information and, where appropriate, publish individual life histories with DOIs. The storage of such synthesized lifetime stories of wild animals under a UAID (unique identifier or ‘animal passport’) will support basic science, conservation efforts and public participation.

ABSTRACT Introduction Healthcare providers' role in co‐creating health interventions and implementation strategies has evolved significantly, and yet, there is little documentation of this from low‐resource settings. This study aims to share the dilemmas of engaging healthcare providers in co‐creating locally adapted clinical guidelines for maternity facilities in Dar es Salaam, Tanzania, and strategies used to address them. Methods An ethnographic study explored the co‐creation of locally adapted clinical guidelines for childbirth care within five maternity facilities in Dar es Salaam. Participant observations were conducted during 11 co‐creation workshops. Six in‐depth interviews explored participant experiences. Data were analyzed using Attride‐Stirling's thematic network analysis framework. Results The analysis revealed four themes representing dilemmas in the co‐creation process and strategies to improve co‐creation: (i) navigating diverse contexts: adapting a single set of guidelines to various, diverse facilities was challenging; this was addressed through engaging in dialogue and flexibility while adjusting care practices. (ii) Competing knowledge systems and sources: differing knowledge sources between researchers and healthcare providers challenged discussions on recommended practices. However, validating scientific recommendations with practical care experience in this context helped bridge this gap. (iii) Fostering meaningful participation: participation was time‐consuming for some. However, early stakeholder engagement and facility‐led participant selection facilitated the meaningful involvement of healthcare providers. (iv) Power imbalances: power dynamics influenced the co‐creation process; involving stakeholders in planning and co‐facilitating workshops helped mitigate these imbalances and encourage more equal participation. Conclusion Navigating contextual variation, differences in knowledge systems, meaningful participation and power dynamics were key challenges in the co‐creation process. However, reflexivity, open and honest dialogue with stakeholders and early engagement enhanced the co‐creation process. Co‐creating locally adapted clinical guidelines with frontline healthcare workers and scientific experts is essential for feasibility and safety. Further research is needed to explore context specificity, decision‐making and the efficacy of co‐creation in low‐resource settings. Patient or Public Contribution Healthcare providers and health managers from five maternity facilities who participated in the co‐creation process were actively involved in this study by providing their consent to be interviewed about their experiences of participation. Clinical Trial Registration This study is a substudy within the PartoMa project. PartoMa is a registered clinical trial with the trial registration number NCT04685668. PartoMa's date of initial trial registration is 28 December 2020.

Abstract Annually, approximately 1.5 million tonnes of sediment are dredged from federal navigational channels in Lake Erie. Recognizing the potential influence of Lake sediments on soil compaction, structure, water retention capacity, and aeration, this research assessed the agronomic performance of selected specialty crops under varying sediment ratios in an open‐field production system. The experimental design involved three sediment application rates: 0 tonne (100% farm soil), 0.7 tonne (90% farm soil and 10% sediment), and 7 tonnes per bed (100% sediment). Lettuces (Lactuca sativa L.) were harvested 35 days after planting, with assessments including fresh and dry weights of leaves root biomass and root length measurements. Radishes (Raphanus sativus L.) were evaluated for root length, leaf fresh weight, root fresh weight, and diameter. Tomatoes (Solanum lycopersicum L.) plants were monitored for plant height and stem diameter. Fruit harvest occurred at days 70 and 75 post‐transplant. Metrics such as total number of marketable fruits, total fruit weight, number of US grade‐1 fruits, and polar and equatorial diameters were recorded. The results revealed significant positive effects of the 7‐tonne sediment treatment on lettuce, including increased dry leaf and root biomass, root lengths, and fresh weight. Similarly, radishes exhibited enhanced weight and length when grown in beds with 7 tonnes of sediment. Tomatoes from the 7‐tonne sediment treatment displayed higher values in plant measurements and harvested fruits. Overall, the findings indicate that soils treated with Lake Erie sediment positively influence the development and production of lettuce, radishes, and tomatoes compared to untreated soils.

Abstract A high percentage of island floras are at risk of extinction and have been reduced to relic populations, often in remote hard‐to‐reach areas. Uncrewed aircraft systems (UAS aka drones) are now being utilized to assist in the survey and collection of rare plants in inaccessible areas or vertical cliff habitats. Here, we test the application of this technology for conservation of 23 plant taxa in three oceanic island hotspots: Hawaiʻi, Madeira and the Republic of Palau. We collect high‐resolution imagery using a small UAS to document the distribution and abundance of vascular flowering plants. Location information is then used to map and assess plant populations. Depending on the terrain, collections are completed using either traditional rope techniques or newly developed remote drone‐based collection methods. Over the course of 6 years, we have greatly expanded our knowledge of rare and endangered species, while increasing survey efficiency and staff safety. Most importantly, this work has had a large impact on the conservation of critically endangered plants. Although using drones for botanical conservation comes with limits and challenges, we see great potential in the continued employment of these techniques wherever plants are growing on cliffs or in other hard‐to‐reach areas.

Abstract Titin‐dependent stiffening of cardiomyocytes is a significant contributor to left ventricular (LV) diastolic dysfunction in heart failure with preserved LV ejection fraction (HFpEF). Small heat shock proteins (HSPs), such as HSPB5 and HSPB1, protect titin and administration of HSPB5 in vitro lowers cardiomyocyte stiffness in pressure‐overload hypertrophy. In humans, oral treatment with geranylgeranylacetone (GGA) increases myocardial HSP expression, but the functional implications are unknown. Our objective was to investigate whether oral GGA treatment lowers cardiomyocyte stiffness and attenuates LV diastolic dysfunction in a rat model of the cardiometabolic syndrome. Twenty‐one‐week‐old male lean (n = 10) and obese (n = 20) ZSF1 rats were studied, and obese rats were randomized to receive GGA (200 mg/kg/day) or vehicle by oral gavage for 4 weeks. Echocardiography and cardiac catheterization were performed before sacrifice at 25 weeks of age. Titin‐based stiffness (Fpassive) was determined by force measurements in relaxing solution with 100 nM [Ca2+] in permeabilized cardiomyocytes at sarcomere lengths (SL) ranging from 1.8 to 2.4 μm. In obese ZSF1 rats, GGA reduced isovolumic relaxation time of the LV without affecting blood pressure, EF or LV weight. In cardiomyocytes, GGA increased myofilament‐bound HSPB5 and HSPB1 expression. Vehicle‐treated obese rats exhibited higher cardiomyocyte stiffness at all SLs compared to lean rats, while GGA reduced stiffness at SL 2.0 μm. In obese ZSF1 rats, oral GGA treatment improves cardiomyocyte stiffness by increasing myofilament‐bound HSPB1 and HSPB5. GGA could represent a potential novel therapy for the early stage of diastolic dysfunction in the cardiometabolic syndrome.

Key Clinical Message This rare diagnosis highlights the importance of anatomical and embryological knowledge in the differential diagnosis of neck masses. Abstract A 41‐year‐old woman was referred to the head and neck surgery department because of a large midline neck mass at the level of the hyoid bone that was diagnostic for functioning thyroid tissue in a totally ectopic location.

Abstract Background The use of virtual platforms for clinical meetings has become the default approach during this pandemic era. Organising an offline conference during a pandemic is a challenge and is possible if the participating crowd is vaccinated and is willing to follow appropriate pandemic protocols. Objective To determine the feasibility of conducting a conference among mostly vaccinated delegates using standard precautionary protocols. Methods This study was conducted at IADVL MIDDERMACON 2021, held in Mangalore, India, in late October 2021, during the phase of decline of the Delta variant of SARS‐CoV‐2. The study population included all conference attendees, including support staff. Details were collected about their vaccination status, comorbidities, and mode of travel to the conference venue. An reverse‐transcription polymerase chain reaction (RT‐PCR) test was done randomly among the attendees for COVID‐19 infection. A post‐conference assessment and RT‐PCR tests were done at the end of 2 weeks to assess the occurrence of infections among study participants. Results A total of 1744 people were present at the venue, of which 576 (33.03%) participated in the study. The percentage of fully vaccinated was 88.88% (512/576). The majority had taken the vaccine Covishield (manufactured by AstraZeneca), that is, 85.06% (490/576). Infection post the conference was reported in 0.195% (1/576). Conclusions Holding large gatherings like medical conferences pose a challenge during a pandemic. However, to increase the benefits of the conference, it is advisable to hold them offline with vaccinated delegates, follow the advice of the conference organising committee, and practise safe precautionary measures.

Abstract Purpose Surgical options for pectoralis major tendon tears include primary repair, though there is no consensus as to which constructs are biomechanically superior for repair. Methods A systematic review was performed by searching PubMed, the Cochrane library, and Embase using PRISMA guidelines to identify studies that analyzed the biomechanical properties of bone tunnels (BT), cortical buttons (CB) and suture anchors (SA) techniques for pectoralis major tendon repair. The search phrase implemented was ‘pectoralis major tendon repair biomechanics’. Studies that did not evaluate biomechanical outcome data, evaluated partial pectoralis major tendon tears, and non‐English articles were excluded. Evaluated outcomes included ultimate load to failure (N) and stiffness (N/mm). Results Six studies met inclusion criteria, including a total of 124 cadaveric specimens, for pectoralis major tendon repair comparing BT with SA and CB. Pooled analysis from four studies reporting on ultimate load to failure between BT and SA failed to reveal a difference between BT and SA (p = 0.489). Pooled analysis from two studies reporting on stiffness failed to reveal a difference in favor of BT compared to SA (p = 0.705). Pooled analysis from four studies reporting on ultimate load to failure between BT and CB failed to reveal a difference between BT and CB (p = 0.567). Pooled analysis from two studies reporting on stiffness failed to reveal a difference in favor of BT compared to CB (p = 0.701). Conclusions There was no difference in load to failure or stiffness when using BT, CB, or SA in pectoralis major tendon repairs. This review reveals that clinical outcomes may better inform which fixation construct to implement in pectoralis major tendon repairs. Level of evidence I.

Key Clinical Message There is a high association between umbilical cord hemangiomas or cysts with fetal mortality. However, favorable outcome is possible with proper prenatal monitoring and care Abstract Umbilical cord hemangiomas are rare neoplasms of vascular origin, commonly found in the free section of the umbilical cord proximal to placental insertion. They are associated with an increased risk of fetal mortality. We present a rare co‐occurrence of an umbilical cord hemangioma and a pseudocyst managed conservatively, with favorable fetal outcome despite the interval increase in size, decreased caliber of the umbilical arteries, and fetal chest compression.

Abstract Papillary thyroid carcinoma (PTC) primarily located in the pyramidal lobe of the thyroid gland is extremely rare, therefore the clinical and pathological features are not well understood. The authors describe a case of PTC of the pyramidal lobe, in a 77‐year‐old woman who underwent en bloc total thyroidectomy with pyramidal lobe, hyoid bone and cervical lymph node excision. In line with the present case, current literature reports a greater presence of worse prognostic factors, namely extrathyroidal extension, advanced T stage or presence of cervical lymph node metastasis. Recently, a new classification has been suggested—Upper Neck Papillary Thyroid Cancer (UPTC)—which encompasses these carcinomas, Delphi ganglion metastases and thyroglossal duct cyst carcinomas, with potential clinical and therapeutic implications, particularly the need for orthotopic thyroidectomy. Also, the complete excision of the pyramidal lobe during thyroidectomy may influence the success of radioactive iodine therapy and the patient's follow‐up surveillance.

N6‐methyladenosine (m6A) and its regulatory proteins have been associated with tumorigenesis in several cancer types. However, knowledge on the mechanistic network related to m6A in bladder cancer (BlCa) is rather limited, requiring further investigation of its functional role. We aimed to uncover the biological role of m6A and related proteins in BlCa and understand how this influences tumor aggressiveness. N6‐adenosine‐methyltransferase catalytic subunit (METTL3), N6‐adenosine‐methyltransferase noncatalytic subunit (METTL14), protein virilizer homolog (VIRMA), and RNA demethylase ALKBH5 (ALKBH5) had significantly lower expression levels in BlCa compared to that in normal urothelium. METTL14 knockdown led to disruption of the remaining methyltransferase complex and a decrease in m6A abundance, as well as overall reduced tumor aggressiveness (decreased cell invasion and migration capacity and increased apoptosis). Furthermore, in vivo, METTL14 knockdown caused tumor size reduction. Collectively, we propose methyltransferase METTL14 as a key component for m6A RNA deposit and that it is closely related to BlCa progression, playing an important role in tumor aggressiveness. These data contribute to a better understanding of the m6A writer complex, which might constitute an appealing therapeutic target.

Abstract Whole‐room indirect calorimeters (WRICs) provide accurate instruments for the measurement of respiratory exchange, energy expenditure, and macronutrient oxidation. Here, we aimed to determine the validity and reproducibility of a 7500 L WRIC for the measurement of ventilation rates and resting metabolic rate (RMR). Technical validation was performed with propane combustion tests (n = 10) whereas biological reproducibility was tested in healthy subjects (13 women, 6 men, mean ± SD age 39.6 ± 15.3) in two 60 min measurements separated by 24 h. Subjects followed a run‐in protocol prior to measurements. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for ventilation rates of O2 (VO2), CO2 (VCO2), the respiratory quotient (RQ; VCO2/VO2), and RMR. Technical validation showed good validity with CVs ranging from 0.67% for VO2 to 1.00% for energy expenditure. For biological reproducibility, CVs were 2.89% for VO2; 2.67% for VCO2; 1.95% for RQ; and 2.68% for RMR. With the exception of RQ (74%), ICCs were excellent for VO2 (94%), VCO2 (96%) and RMR (95%). Excluding participants that deviated from the run‐in protocol did not alter results. In conclusion, the 7500 L WRIC is technically valid and reproducible for ventilation rates and RMR.

Abstract Purpose Hormone replacement therapy (HRT) causes a significant increase in the risk of venous thrombosis. The risk of medical and surgery‐related complications among women taking HRT following total hip arthroplasty (THA) is poorly understood, and there are currently no guidelines in place regarding venous thromboembolism prophylaxis in this patient population. The purpose of this study was to evaluate the frequency of early medical and surgery‐related complications following THA among women taking HRT. Methods Women aged > 40 years of age who underwent primary THA were identified from a retrospective database review. A control group of non‐HRT users was matched using propensity scoring to HRT users. Rates of 90‐day medical complications and 1‐year surgery‐related complications were compared between cohorts using odds ratios. Postoperative anticoagulation regimens were also compared. Results There were 3,936 patients in the HRT cohort who were matched to 39,360 patients not taking HRT. There were no significant differences in rates of DVT (OR 0.94, p = 0.6601) or PE (OR 0.80, p = 0.4102) between cohorts. Patients on HRT were more likely to sustain a dislocation (OR 1.35, p = 0.0269) or undergo revision surgery (OR 1.23, p = 0.0105). HRT patients were more likely to be prescribed warfarin (OR 1.21, p = 0.0001) or enoxaparin (OR 1.18, p = 0.0022) and less likely to be prescribed rivaroxaban (OR 0.62, p

Abstract Purpose Robotic total knee arthroplasty (TKA) has seen a rapid increase in utilization with recent literature suggesting that implant accuracy and resection are better optimized than in conventional TKA. The purpose of this study was to evaluate the biomechanical properties of robotic‐assisted versus conventional TKA in minimizing biplanar femoral and tibial resection error in cadaveric specimens. Methods A systematic review and meta‐analysis was performed by searching through PubMed, Cochrane library, and Embase to identify studies that analyzed the biomechanical properties of robotic assisted and conventional TKA, according to standard PRISMA guidelines. Evaluated outcomes included femoral coronal resection error (deg), femoral sagittal resection error (deg), tibial coronal resection error (deg), and tibial sagittal resection error (deg). Results Seven studies met inclusion criteria, including a total of 140 cadaveric specimens (robotic: 70, conventional: 70), for resection accuracy between robotic and conventional TKA. Pooled analysis from seven studies revealed a significant difference in femoral coronal and sagittal resection error in favor of robotic systems compared to conventional systems (p

Testicular germ cell tumors (TGCTs) are the most common cancers in men aged 15–39 years and are divided into two major groups, seminomas and nonseminomas. Novel treatment options are required for these patients, to limit side effects of chemotherapy. We hypothesized that promoter methylation of relevant homologous recombination (HR) genes might be predictive of response to poly‐ADP ribose polymerase inhibitors (PARPis) in TGCTs. We report a study pipeline combining in silico, in vitro, and clinical steps. By using several databases and in silico tools, we identified BRCA1, RAD51C, PALB2, RAD54B, and SYCP3 as the most relevant genes for further investigation and pinpointed specific CpG sites with pronounced negative correlation to gene expression. Nonseminomas displayed significantly higher methylation levels for all target genes, where increased methylation was observed in patients with more differentiated subtypes and higher disease burden. We independently performed second‐line targeted validation in tissue series from TGCT patients. A moderate and/or strong anti‐correlation between gene expression (assessed by RNA‐sequencing) and promoter methylation (assessed by 450k array) was found, for all of the targets. As a proof of concept, we demonstrated the sensitivity of TGCT cell lines to Olaparib, which associated with differential methylation levels of a subset of targets, namely BRCA1 and RAD51C. Our findings support the use of HR genes promoter methylation as a predictor of the therapeutic response to PARPis in patients with TGCT.

Abstract Background Cancer cachexia is a condition often seen at diagnosis, throughout anti‐cancer treatments and in end‐stage non‐small‐cell lung cancer patients. Methods and results Participants with late‐stage non‐small‐cell lung cancer and cachexia (defined as ≥5% weight loss within 12 months) were randomly assigned 1:2 to 2.09 g of eicosapentaenoic acid (EPA) and 300 mg of cyclo‐oxygenase‐2 inhibitor celecoxib orally once daily vs. same dosing of EPA, celecoxib, plus two sessions per week of progressive resistance training and 20 g of oral essential amino acids high in leucine in a split dose over 3 days, after each session. Primary endpoint was the acceptability of the earlier multi‐targeted approach. Main secondary endpoints included change in body weight and fat‐free mass, by bioelectric impedance analysis and total quadriceps muscle volume by magnetic resonance imaging over 20 weeks. Sixty‐nine patients were screened resulting in 20 patients being enrolled. Acceptability scored high, with 4.5/5 (Arm A) and 5/5 (Arm B) for EPA and 5/5 for celecoxib within both arms and 4.8/5 for progressive resistance training sessions and 4.5/5 for essential amino acids within Arm B, all at Week 20. Results showed a net gain in bioelectric impedance analysis fat‐free mass of +1.3 kg, n = 2 (Arm A), compared with +0.7 kg, n = 7 (Arm B) at Week 12, and —1.5 kg, n = 2 (Arm A), compared with —1.7 kg, n = 4 (Arm B) at Week 20. Trends in efficacy in terms of improvement and/or stability in cachexia markers were seen within magnetic resonance imaging muscle volume, albumin, and C‐reactive protein levels within both arms. There were no exercise‐related adverse events, with one possible related adverse event of asymptomatic atrial fibrillation in one participant within Arm A. Conclusions Non‐small‐cell lung cancer cachectic patients are willing to be enrolled onto a multi‐targeted treatment regimen and may benefit from cachexia symptom management even during the late/refractory stage.

Objective Quality of life (QOL) and quality of care (QOC) in systemic lupus erythematosus (SLE) remains poor. Satisfaction with care (SC), a QOC surrogate, correlates with health behaviors and outcomes. This study aimed to determine correlates of SC in SLE. Methods A total of 1262 patients with SLE were recruited from various countries. Demographics, disease activity (modified Systemic Lupus Erythematosus Disease Activity Index for the Safety of Estrogens in Lupus Erythematosus: National Assessment trial [SELENA‐SLEDAI]), and QOL (LupusPRO version 1.7) were collected. SC was collected using LupusPRO version 1.7. Regression analyses were conducted using demographic, disease (duration, disease activity, damage, and medications), geographic (eg, China vs United States), and QOL factors as independent predictors. Results The mean (SD) age was 41.7 (13.5) years; 93% of patients were women. On the univariate analysis, age, ethnicity, current steroid use, disease activity, and QOL (social support, coping) were associated with SC. On the multivariate analysis, Asian participants had worse SC, whereas African American and Hispanic patients had better SC. Greater disease activity, better coping, and social support remained independent correlates of better SC. Compared with US patients, patients from China and Canada had worse SC on the univariate analysis. In the multivariate models, Asian ethnicity remained independently associated with worse SC, even after we adjusted for geographic background (China). No associations between African American or Hispanic ethnicity and SC were retained when geographic location (Canada) was added to the multivariate model. Canadian patients had worse SC when compared with US patients. Higher disease activity, better social support, and coping remained associated with better SC. Conclusion Greater social support, coping, and, paradoxically, SLE disease activity are associated with better SC. Social support and coping are modifiable factors that should be addressed by the provider, especially in the Asian population. Therefore, evaluation of a patient's external and internal resources using a biopsychosocial model is recommended. Higher disease activity correlated with better SC, suggesting that the latter may not be a good surrogate for QOC or health outcomes.

Abstract Background The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervous system. Therefore, early diagnosis of the affected individuals is important, as it can prevent clinical manifestations of the disease. Methods In this report, the biochemical and genetic findings performed in 223 patients diagnosed through the Portuguese Neonatal Screening Program (PNSP) are presented. Results Overall, the results show that a high overlap exists between different types of variants and phenylalanine levels. Molecular analyses reveal a wide mutational spectrum in our population with a total of 56 previously reported variants, most of them found in compound heterozygosity (74% of the patients). Intragenic polymorphic markers were used to assess the haplotypic structure of mutated chromosomes for the most frequent variants found in homozygosity in our population (p.Ile65Thr, p.Arg158Gln, p.Leu249Phe, p.Arg261Gln, p.Val388Met, and c.1066‐11G>A). Conclusion Our data reveal high heterogeneity at the biochemical and molecular levels and are expected to provide a better understanding of the molecular basis of this disease and to provide clues to elucidate genotype–phenotype correlations.

Abstract Background The Oculo‐Auriculo‐Vertebral Spectrum (OAVS) or Goldenhar Syndrome is an embryonic developmental disorder characterized by hemifacial microsomia associated with auricular, ocular and vertebral malformations. The clinical heterogeneity of this spectrum and its incomplete penetrance limited the molecular diagnosis. In this study, we describe a novel causative gene, ZYG11B. Methods A sporadic case of OAVS was analyzed by whole exome sequencing in trio strategy. The identified candidate gene, ZYG11B, was screened in 143 patients by next generation sequencing. Overexpression and immunofluorescence of wild‐type and mutated ZYG11B forms were performed in Hela cells. Moreover, morpholinos were used for transient knockdown of its homologue in zebrafish embryo. Results A nonsense de novo heterozygous variant in ZYG11B, (NM_024646, c.1609G>T, p.Glu537*) was identified in a single OAVS patient. This variant leads in vitro to a truncated protein whose subcellular localization is altered. Transient knockdown of the zebrafish homologue gene confirmed its role in craniofacial cartilages architecture and in notochord development. Moreover, ZYG11B expression regulates a cartilage master regulator, SOX6, and is regulated by Retinoic Acid, a known developmental toxic molecule leading to clinical features of OAVS. Conclusion Based on genetic, cellular and animal model data, we proposed ZYG11B as a novel rare causative gene for OAVS.