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Penelitian ini bertujuan untuk mengetahui manajemen talenta berbasis religius melalui kepiawaian Wali Asuh Pondok Pesantren Nurul Jadid dalam meningkatkan kualitas intelektual dan religius santri-santri untuk mewujudkan pesantren yang mempunyai keunggulan dibidang akademik maupun dibidang keagamaan dan sosial kemasyarakatan. Penelitian ini menggunakan pendekatan kualitatif jenis studi kasus. Pengumpulan data penelitian dilakukan dengan observasi, wawancara dan dokumentasi. Penelitian ini dilakukan pada santri yang bertalenta religius melalui kepiawaian Wali Asuh Pondok Pesantren Nurul Jadid. Hasil penelitian menunjukkan bahwa dalam upaya meningkatkan talenta santri berbasis religius melalui kepiawaian Wali Asuh Pondok Pesantren Nurul Jadid ialah dengan melalui pendekatan secara personal approach, sharing, pembiasaan dengan melembagakan program tersebut dijadikan program rutinitas. Sehingga hal tersebut pesantren dapat berkembang melalui santri yang bertalenta religius melalui kepiawaian Wali Asuh.

Background/Aim: From accurate diagnostics to personalised treatment plans, artificial intelligence (AI) has the potential to revolutionise healthcare. The abundance of medical data has led to AI being employed for accurate diagnoses, treatment protocols and patient care. Students' perception of AI integration in medical education is crucial for its successful implementation. This study aimed to assess the acceptance and understanding of AI integration among students in medical education across different regions of India through a cross-sectional observation. Methods: A pan-India survey was conducted among medical students between 1 August 2023 to 20 August 2023 with a pre-validated questionnaire covering AI awareness and understanding through Google Form, circulated via WhatsApp. Results: A total of 730 medical students completed the survey of which 58.6 % were males and 41.4 % were females. Most students (80.7 %) knew about AI, but 53.6 % had limited awareness of AI in medicine. Opinions on AI integration was diverse, with 46.8 % in favour. Workshops (45.2 %) and lectures (31.1 %) were preferred learning formats. Students were interested in various AI topics and expect AI to positively impact medicine (45.9 %). Radiology, surgery and general medicine were predicted to be most influenced by AI. Concerns about overreliance on AI (49.2 %) and lack of empathy (43.7 %) were highlighted. Conclusions: Medical students in India display a keen interest in AI and its integration into medical education. To fully harness AI's potential in healthcare, comprehensive AI curricula and faculty training are needed. Students are aware of the challenges and opportunities, emphasising the importance of balanced AI adoption in medical practice and education.

Genetic improvement of tea through breeding is difficult. Therefore, transgenic tea plants expressing the osmotin gene from Nicotiana tabacum were produced using parameters optimised for biolistic-gun mediated transformation. During optimisation, a total of 4,500 somatic embryos were bombarded using nine combinations of variable target distances and burst pressures, while keeping the gap distance (0.6 cm) and macrocarrier flight distance (16 mm) constant. A total of 90 independent, PCR-positive lines were generated. Southern hybridisation confirmed integration of the osmotin gene in 26 out of 27 PCR-positive lines (three independent lines from each of the nine parameter combinations were selected at random). Statistical analysis revealed that the efficiency of transgene integration was significantly affected by target distance. Only those lines derived from somatic embryos bombarded with 1.0 pg plasmid DNA using a 7.58 MPa burst pressure and 9-cm target distance showed osmotin expression. This was evident from strong northern hybridisation and RT-PCR signals. Leaves of 4-year-old transgenic plants growing in a contained polythene tunnel showed improved osmotic adjustment in response to osmotic stress imposed by NaCl. The osmotic potentials of transgenic leaves immersed in 100 mM or 200 mM NaCl solutions were more negative than those of non-transformed control leaves. [ABSTRACT FROM AUTHOR]

【Abstract】Objective: Management of Rockwood type 3 acromioclavicular disruptions is a matter of debate. Should we adopt conservative or operative measures at first presentation? It is not clear but most of the evidences are in favour of conservative management. We present our expe-rience in managing these patients surgically. Methods: We present a prospective series of eight cases of chronic Rockwood type 3 acromioclavicular joint disruptions treated surgically. Anatomical reconstruction of the coracoclavicular ligament was done by artificial braided polyester ligament prosthesis. Results: All the patients were able to perform daily activities from an average of the 14th postoperative day. All patients felt an improvement in pain, with decrease in ave-rage visual analogue scale from preoperative 6.5 points (range 3-9 points) to 2.0 points (range 0-5 points), Constant score from 59% to 91% and American Shoulder and Elbow Surgeons shoulder score from 65 to 93 points postoperatively. These results improved or at least remained stationary on midterm follow-up, and no deterioration was recorded at an average follow-up of 46 months. Conclusion: This midterm outcome analysis of the artificial ligament prosthesis is the first such follow-up study with prosthesis. Our results are encouraging and justify the further use and evaluation of this relatively new and easily reproducible technique. Key words: Acromioclavicular joint; Prostheses and implants; Reconstructive surgical procedures; Ligaments

【Abstract】High-grade spondylolisthesis is very rare. We came across a case of high-grade spondylolisthe-sis at the L5-S1 level in a 32-year-old manual labourer who was hit by a heavy object on his flexed back. The patient presented to us with persistent deformity in the back. He complained of back pain on prolonged standing and after moderate work. Because of that he was unable to return to his work. On clinical examination there was a large step in the lower lumbar region. Detailed neurological evaluation of the lower limbs did not reveal any sensory or motor deficit, neither did bowel or bladder involvement. Radiographic examination showed L5 over S1 traumatic spondyloptosis. CT scan revealed that neural canal was in normal width. MRI confirmed spondyloptosis of L5 over S1 without any compromise of the spinal canal and with normal-looking cauda. Concerning the delayed presentation and no neuro-logical deficit, the patient was managed conservatively af-ter thorough counsel. At 6 months, the patient returned to his work and at the latest follow-up (15 months) he was free from back pain. Conservative means of treatment can lead to satisfactory outcome, especially when the patient has delayed presentation. Key words: Spine; Spondylolisthesis; Back pain

【Abstract】Objective: To assess the outcome of immediate plate osteosynthesis via application of antibiotic impregnated collagen fleeces (gentamicin-collagen and antibiotic sponge) which gradually release antibiotic locally in the surgical treatment of open fractures presented to us 6 hours after injury. Methods: All cases were treated in our tertiary level trauma center and teaching hospital including 35 patients with open fractures who were treated by immediate open reduction and plate fixation from January 2008 to August 2010. Among them, 31 patients were available for adequate follow-up and assessment. All fractures were treated by irrigation and debridement, immediate open reduction and plate fixation along with placement of antibiotic-releasing collagen fleeces around the plate just before closure of wound. Patients were assessed to determine postoperative infection, delayed union or nonunion and development of other postoperative complications. It was hypothesized that immediate plate osteosynthesis after thorough debridement and local antibiotics would give safe and acceptable clinical re- sults in treatment of open fractures. Results: The 31 patients with adequate final follow-up were assessed at a mean time of 40 weeks (15-160 weeks). Most fractures united primarily in an acceptable time period according to area of involvement. Local wound complications (superficial infection and skin loss) were found in 3 patients (9.67%). Deep infection was noted in 2 patients (6.45%). None of these patients needed implant removal and both fractures united in due time. Delayed union was noted in 5 patients (16.13%). No patient progressed to non- union or implant failure in long term follow-up. Excessive scarring was developed in 2 patients (6.45%). Conclusions: Immediate plate osteosynthesis after adequate debridement and placement of collagen film eluting antibiotics locally produces excellent results regarding bone union and absence of deep infections and is a safe technique in the management of open bone injuries. These sponges can be used easily with any form of internal fixation and there is no need of second surgery for the removal of these antibiotic carriers since they are bioabsorbable. Local antibiotic-impregnated collagen sponges along with systemic antibiotics for 3 to 5 days offer promising results in open fracture management. Key words: Fractures, open; Debridement; Fracture fixation, internal; Collagen

【Abstract】Intraarticular nonunion of tibial plateau is rare. In the literature, only 9 patients were found to be treated for intraarticular tibial plateau nonunion and they got varying results. Internal fixation along with bone grafting was done as a standard treatment in all cases. We treated 4 different profile cases of intraarticular tibial plateau nonunion in our institution by 4 different methods. We treated these cases with plaster of paris cast, internal fixation along with bone graft, arthrodesis with K-nail and total knee replacement. Case 1 was treated with plaster of paris (POP) cast as the patient refused surgery. The fracture was united and the patient was fully satisfied with full range of motion despite valgus malalignment. Case 2 was managed with open reduction internal fixation along with bone grafting. The patient had a good union and got full range of motion at the knee joint. Case 3 was treated with total knee arthroplasty due to her old age and got satisfactory result. Case 4 was an infected nonunion. Arthrodesis was done and the patient could walk with full weight bearing independently. We conclude that internal fixation along with bone grafting may not be suitable in all cases of intraarticular nonunion of tibial plateau. Causes of nonunion, present condition and range of motion of the knee joint, as well as the age of patient should be all considered and the treatment should be individualised according to each patient抯 situation. Key words: Intra-articular fractures; Arthrodesis; Fracture fixation, internal

【Abstract】Breakage of locking bolts is an impor- tant cause of interlocking nail failure in femoral fractures. It usually occurs in the form of single breakage in one of the distal bolts of the nail or nail breakage around the distal locking hole. Here we report an unusual case of intramedul- lary femoral nail failure with segmental breakage of both the distal locking bolts. Such a scenario usually complicates further management. We successfully managed this case with exchange nailing without bone grafting. Here we briefly reviewed the literature regarding such an unusual presenta- tion and discussed in detail the possible etiology of such a presentation and the management options when facing such a complex situation. Key words: Femoral fractures; Bone screws; Frac- ture fixation, intramedullary; Fracture healing

【Abstract】Intramedullary interlocking nailing is a gold standard for treatment of tibial shaft fractures. Bending of a nail secondary to trauma is a rare complication, which may be encountered in healed or unhealed tibial shaft fractures. Removal of such bent nail is always a challenge. We reported this case to discuss various techniques for removal of bent nails and to share our experience in removing a bent tibial intramedullary nail in a 30-year-old man, who was admitted in our department with re-fracture of the right tibial shaft due to a roadside accident two years after the initial surgical treatment. The intramedullary nail, bent by 30 degrees and visible on anterioposterior as well as on lateral radiographs, was firstly weakened by partially cutting the convex wall, then straightened by applying external force, and finally removed by using the standard nail removal method. Key words: Fracture fixation, intramedullary; Tibial fractures; Device removal

【Abstract】Hoffa fracture is an uncommon injury. In the literature, lateral condylar Hoffa fracture is mentioned as a more common injury pattern than medial condylar Hoffa fracture. The mechanism of injury and method of treatment is not very well described in the literature. We are present- ing a rare case of comminuted medial condylar Hoffa frac- ture with ipsilateral patellar fracture. The mechanism of in- jury has not been described in the literature. Lag screw fixation, which is the most acceptable method of treatment, is not possible due to comminution. We explain the pos- sible mechanism of injury and fix the fracture with L-but- tress plate. Key words: Fractures, bone; Knee joint; Femur; Pa- tella

Children with recurrent/metastatic neuroblastoma (NB) have a dismal survival (<25%). Novel therapies are desperately needed. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is highly expressed on NB. C021 is a selective oncolytic herpes simplex virus modified to overexpress human interleukin-21 (hIL-21), a cytokine that enhances natural killer (NK) cell cytotoxicity. In the current study, we successfully engineered ex - vivo -expanded NK cells to express a chimeric antigen receptor (CAR) against ROR1 using mRNA electroporation and investigated the efficacy of anti-ROR1-CAR-NK cells combined with C021 in targeting ROR1 + NB. We found that C021-infected NB cells secreted hIL-21 in vitro and in vivo . Compared to the non-cytokine-secreting parental virus C134, C021 significantly enhanced the in vitro cytotoxicity ( p  < 0.05) of anti-ROR1-CAR-NK cells with increased interferon (IFN)-γ ( p  < 0.05), granzyme B ( p  < 0.05), and perforin ( p  < 0.05) secretion against NB cells. Furthermore, the combination of C021 and anti-ROR1-CAR-NK cells significantly extended the survival of human NB xenografted NSG mice compared to controls (mock NK, ROR1-CAR-NK, C134, C021, C134+ROR1-CAR-NK, and C021+mock NK). Our results suggest that cytokine-secreting oncolytic virus in combination with CAR-NK cells is a novel, effective immunotherapeutic approach for high-risk NB., Competing Interests: This work was presented in part at the Pediatric Transplantation & Cellular Therapy Consortium (2023), Fort Worth, TX; International Society for Cell & Gene Therapy (2022), San Francisco, CA; and Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy (2022), Salt Lake City, Utah. M.S.C. has served as a consultant for Jazz Pharmaceuticals, Omeros Pharmaceuticals, Servier Pharmaceuticals, Abbvie, and Novartis Pharmaceuticals; on speakers bureau for Jazz Pharmaceuticals, Servier Pharmaceuticals, Amgen, Inc., Sanofi, and Sobi; and on the advisory board for Astra Zeneca and has received research funding from Celularity, Merck, Miltenyi Biotec, Servier, Omeros, Jazz, and Janssen. D.A.L. reports personal fees and other fees from Kiadis Pharma, CytoSen Therapeutics, Courier Therapeutics, and Caribou Biosciences outside the submitted work. In addition, D.A.L. has a patent broadly related to NK cell therapy of cancer with royalties paid to Kiadis Pharma. T.P.C. recently served as a one-time consultant to Blueprint, Incyte, and Oncopeptides and a DSMB chair for SpringWorks and is a cofounder of Vironexis Biotherapeutics, Inc., (© 2024 The Authors.)

Objective: Comorbidities between internalizing disorders (IDs) and functional disorders (FDs) are well-documented, indicating shared pathways. However, their symptom-level relationships have been largely unexplored. This exploratory study employs a network approach to investigate symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS) to identify bridge symptoms explaining comorbidity between the two domains., Methods: We used cross-sectional data on 72,919 adult subjects from the Lifelines Cohort Study, a Dutch general population sample. A total of 38 symptoms representing diagnostic criteria of IDs and FDs were assessed with validated questionnaires. Network models were estimated using eLasso, based on the Ising model, to identify bridge symptoms. The Network Comparison Test (NCT) was used to test whether there were differences in network structure and strength across sex and age., Results: Symptoms were moderately connected, with a network density of 52.7%. ID and FD symptoms clustered in their respective domains, but were connected through the bridge symptoms, fatigue, difficulty concentrating, trouble sleeping, and unrefreshing sleep. Fatigue and difficulty concentrating had the most connections, associated with 86.6% and 78.9% of the other symptoms, respectively. NCTs indicated no differences in network connectivity between females versus males or younger versus older adults (>50 years)., Conclusions: ID and FD symptoms are moderately interconnected. Bridge symptoms displaying strong connections to multiple disorders may play a central role in the mechanisms underpinning the comorbidity between IDs and FDs., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier Inc.)

High-grade gliomas (HGGs) and glioblastomas (GBMs) are the most aggressive and lethal brain tumors. The current standard of care (SOC) includes gross safe surgical resection followed by chemoradiotherapy. The main chemotherapeutic agents are the DNA-alkylating agent temozolomide (TMZ) and adjuvants. Due to the outdated therapeutic protocols and lack of specific treatments, there is an urgent and rising need to improve our understanding of tumor biology and design more effective therapeutic strategies. In vitro models are essential for investigating glioma biology and testing novel therapeutic approaches. While using commercially available and patient-derived glioma cell lines for in vitro studies is common practice, they exhibit several limitations, including failing to maintain the genetic and phenotypic diversity of primary tumors, undergo genetic drift over time, and often lacking the invasive and stem-like characteristics of patient tumors. These limitations can lead to inconsistent and non-reproducible results, hampering translational research progress. In this study, we established a novel primary murine HGG cell line, isolated from an immunocompetent HGG-bearing RCAS/T-va mouse. We characterized the transcriptome and phenotype to ensure that this cell line resembles the nature of HGGs and retains the ability to reprogram primary murine T lymphocytes., Competing Interests: P.R. and K.C. are associate editors of Molecular Therapy Oncology., (© 2024 The Author(s).)

Introduction: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas with unacceptably low cure rates occurring often in patients with neurofibromatosis 1 defects. To investigate oncolytic Herpes Simplex Virus (oHSV) as an immunotherapeutic approach, we compared viral replication, functional activity, and immune response between unarmed and interleukin 12 (IL-12)-armed oncolytic viruses in virus-permissive (B109) and -resistant (67C-4) murine MPNSTs., Methods: This study compared two attenuated IL-12-oHSVs with γ134.5 gene deletions (Δγ134.5) and the same transgene expression cassette. The primary difference in the IL-12-oHSVs was in their ability to counter the translational arrest response in infected cells. Unlike M002 (Δγ134.5, mIL-12), C002 (Δγ134.5, mIL-12, IRS1) expresses an HCMV IRS1 gene and evades dsRNA activated translational arrest in infected cells., Results and Discussion: Our results show that oHSV replication and gene expression results in vitro were not predictive of oHSV direct oncolytic activity in vivo. Tumors that supported viral replication in cell culture studies resisted viral replication by both oHSVs and restricted M002 transgene expression in vivo. Furthermore, two IL-12-oHSVs with equivalent transcriptional activity differed in IL-12 protein production in vivo, and the differences in IL-12 protein levels were reflected in immune infiltrate activity changes as well as tumor growth suppression differences between the IL-12-oHSVs. C002-treated tumors exhibited sustained IL-12 production with improved dendritic cells, monocyte-macrophage activity (MHCII, CD80/CD86 upregulation) and a polyfunctional Th1-cell response in the tumor infiltrates., Conclusion: These results suggest that transgene protein production differences between oHSVs in vivo, in addition to replication differences, can impact OV-therapeutic activity., Competing Interests: JM has the following relationships which may pose or be perceived as posing a financial conflict of interest: he is a board and equity holding member, in Aettis, Inc. and may receive royalties. The company holds frozen oncolytic viral stocks. Mustang Bio Tech is licensing the Intellectual Property IP of C134 an oncolytic viral Therapy. JM is blinded to the conditions for the C134 clinical trials. He is a shareholder for a privately held Small Business Innovation Research LLC, Treovir, Inc., concerning G207 oncolytic viral therapy now in clinical trial. Merck, Inc. provides industry grant support by providing Keytruda pembrolizumab for a clinical trial of M032 oncolytic virotherapy and financial support for a clinical trial. JM is a listee on Intellectual Property 1 related to a cancer immunotherapy system, and 2 to a novel immuno-virotherapeutic strategy targeting the glioma secretome. This IP has been filed by in8Bio formerly Incysus, Ltd. and has royalty earning potential. In the interest of full disclosure, KC receives licensure payments from Mustang Bio for the C134 virus, but there are no relevant financial conflicts for the technology addressed in this paper. 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 Kim, Saini, Kim, Hernandez-Aguirre, Hedberg, Martin, Mo, Cripe, Markert, Cassady and Dhital.)

Introduction  Eagle syndrome is a rare and an often misdiagnosed entity in otorhinolaryngology. Objective  To determine the efficacy of the surgical treatment for Eagle syndrome. Methods  The present prospective study included 25 patients who presented with complaints of pain in the throat, ear, and neck, as well as difficulty and/or pain while swallowing; they were assessed for Eagle syndrome. As per patient profile, we performed a clinical assessments along with orthopantomograms (OPGs), three-dimensional computed tomography (3D CT) scans, and cone beam computed tomography (CBCT). Pain was assessed pre- and postoperatively through the Numerical Rating Scale-11 (NRS-11), whose score ranges from 0 to 10. Microscopic tonsillo-styloidectomy was performed in cases in which the conservative treatment failed to relieve pain. Results  The mean age of the entire study population was of 36.08 ± 7.19 years, and the male-to-female ratio was of 1.08:1. Referred otalgia was the commonest (44%) complaint. Radiologically, out of 25 patients, 20 patients presented elongated styloid processes. The longest symptomatic styloid process measured radiographically was of 64.7 mm while the shortest was of 28.2 mm. Out of 20 patients, 12 underwent surgery. The postoperative pain assessment through the NRS-11 was performed on day 0 (3.83 ± 0.83), day 7 (1.5 ± 0.52), week 4 (0.5 ± 0.52), and week 12 (0.41 ± 0.51). By 12 weeks, 7 patients were symptom-free, while 5 patients still reported mild pain. Conclusion  Eagle syndrome associated with an elongated styloid process is not a rarity, but it often goes undiagnosed. Microscopic tonsillo-styloidectomy shows excellent results in the management of patients with Eagle syndrome., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: Core decompression (CD) is beneficial in the early stage of osteonecrosis of the femoral head (ONFH). Adjunctive bone marrow derived cell therapies (BMDCT) have been advocated which potentially aid the regenerative process., Question/purpose: This study was conducted to determine potential benefit of CD + BMDCT in ONFH, in terms of disease progression, conversion to arthroplasty (primary outcomes), and functional outcomes and complication rates (secondary outcomes)., Methods: A systematic review of literature was performed on 3 databases. Studies reporting CD + BMDCT (intralesional instillation) in ONFH, with a minimum follow up of 1 year and reporting the pre-defined outcome measures were included in the review. Meta-analysis consisted of two different arms: a comparative arm, to compare CD + BMDCT to CD alone, and a non-comparative meta-analysis arm, to determine pooled rates of disease progression, conversion to arthroplasty and complication rates., Results: A total of 18 studies were included in the systematic review. CD + BMDCT had lower rates of disease progression (OR 0.19 [95% CI, 0.09, 0.40]) and conversion to arthroplasty (OR 0.20 [95% CI, 0.11, 0.40]) as compared to CD alone. Functional score (MD = -7.07 [95% CI, -12.28, -1.86]) and visual analog scale also showed better improvement with the use of CD + BMAC (MD = -10.39 [95% CI, -12.87, -7.90]). Increasing age and post-collapse stage at presentation were noted to have an adverse effect on the outcomes., Conclusion: CD + BMDCT was found to decrease disease progression and conversion to arthroplasty, and was noted to have better functional outcome scores as compared to CD alone., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Background: Ovarian clear cell carcinoma (OCCC) accounts for approximately 8-10% of epithelial ovarian cancers in the United States. Although it is rare, OCCC usually presents with treatment challenges and the overall prognosis is far worse than high grade serous ovarian cancer HGSOC. The objective of this study was to examine the therapeutic relevance of combining oncolytic virus with cisplatin for ovarian cancer clear cell carcinoma (OCCC)., Results: We identified that TMEM205, a recently discovered transmembrane protein, contributes to chemoresistance in OCCC cells via the exosomal pathway. Mechanistically, TMEM205 undergoes ligand-independent constitutive endocytosis and co-localizes with Rab11 to contribute to the late recycling endosomes in a clathrin-independent manner. Further, we observed that oncolytic virus (oHSV) pretreatment followed by treatment with cisplatin decreases TMEM205 expression and sensitizes cells to cisplatin in a synergistic manner in OCCC cells. TMEM205 interacts with glycoprotein-C of oHSV post-infection; both of these proteins undergo ubiquitination and ultimately get shuttled outside the cell via exosomes. Thus, we demonstrate the mechanotransduction pathway of TMEM205-mediated chemoresistance along with targeting this pathway using oHSV and cisplatin as a powerful therapeutic strategy for OCCC. oHSV combination with cisplatin inhibits OCCC tumor growth in vivo in immunodeficient and immunocompetent mice models., Conclusion: Our results suggest that the combination of oHSV and cisplatin in immunocompetent as well as immune deficient OCCC tumor bearing mice reduces overall tumor burden as well as metastatic disease thereby providing survival benefit. Additionally, the detection of TMEM205 in exosomal cargo early in OCCC development has potential to be exploited as a biomarker., (© 2022. The Author(s).)

Charcot Foot is often misdiagnosed because of its varied presentation that mimics other common disorders including tubercular rheumatism, complex regional pain syndrome or gout. We present a case of ankle swelling and discuss the differential diagnosis, radiological findings, and management. We also discuss the approach to diagnosis and provide differences in clinical presentations, magnetic resonance imaging,and bone scan findings for various differentials considered for Charcot foot.

India currently ranks the highest in the world with over 3.86 lakhs new COVID-19 cases per day. With a spike in the number of cases in the second wave of COVID-19 in 2021 compared to the first wave of the outbreak in 2020, there have been varied clinical manifestations among masses. This study aimed to determine the changing trends in prevalence of COVID-19 symptoms during the pandemic. A cross-sectional study among 166 individuals was carried out using a self-designed survey-based questionnaire. Two groups were made on the basis of symptoms and compared: Group A- patients who tested COVID-19 positive in 2020 and Group B- patients who tested COVID-19 positive in 2021. 130 participants (78.31%) had tested positive for COVID-19, out of which 110 (84.62%) were symptomatic and 20 (15.38%) were asymptomatic. Fever was the most common presenting symptom (27.69%) followed by difficulty in breathing (24.62%). Group A individuals (n = 37), reported fever as the most common presenting symptom (45.95%), followed by body ache (13.51%); while those in Group B (n = 93) reported difficulty in breathing (33.33%) followed by fever (20.43%). The most common general symptoms were fever and difficulty in breathing while sore throat, cough and anosmia were the most common ENT symptoms. 57.83% had been vaccinated out of which 38.55% experienced symptoms post-vaccination. The prevalence of symptoms in the first and second wave of the pandemic can help in better understanding of the changing symptomatology of SARS-CoV-2 virus., Competing Interests: Conflict of interestNone., (© Association of Otolaryngologists of India 2022.)

Introduction  Patients with a history of or active COVID-19 infection are predisposed to the development of opportunist bacterial and fungal infections. A rising incidence of a rare occurring fungal infection earlier, called mucormycosis, has been reported in abundance across the globe since March 2021, especially in India just as the second wave of COVID-19 began, caused by the trifecta of hyperglycemia (new-onset or exacerbation of pre-existing diabetes), oxygen therapy (invasive or noninvasive ventilation), and prolonged intake of steroids. Objective  The present study aimed at assessing the prevalence of post-COVID mucormycosis in males of younger age group and spread of rhino-orbital-cerebral mucormycosis (ROCM). Methods  A case-control study was performed over a period of 3 months among 60 male patients with confirmed diagnosis of mucormycosis. Individuals < 40 years old were included in the case group ( n  = 30), while those > 40 years old were included as controls ( n  = 30). Disease spread was assessed in three types of ROCM, that is, rhinomaxillary, rhino-orbital, and rhino-orbito-cerebral mucormycosis. Results  In the control group, the mean age was 48.47 years old, the mean HbA1c was 10.62 ± 1.88%, with most of them suffering from rhino-orbital mucormycosis. In the case group, the mean age was 31.57 years old, with a mean HbA1c of 10.11 ± 2.46%, and most patients had rhinomaxillary mucormycosis. The duration of steroid intake and mode of oxygen therapy were found to be significant in the severity of ROCM. Conclusion  Rising cases of post-COVID mucormycosis have brought to light the fatal consequences of prolonged use of steroids and oxygen therapy towards the development and spread of ROCM among young and middle-aged males., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Introduction: TMEM205 is a novel transmembrane protein associated with platinum resistance (PR) in epithelial ovarian carcinoma (OC), however, the specific mechanisms associated with this resistance remain to be elucidated., Methods: TMEM205 expression was evaluated in platinum-sensitive (PS) versus platinum resistant (PR) ovarian cancer cell lines and patient serum/tissues. Exosomal efflux of platinum was evaluated with inductively coupled plasma mass spectrometry (ICP-MS) after pre-treatment with small molecule inhibitors (L-2663/L-2797) of TMEM205 prior to treatment with platinum. Cytotoxicity of combination treatment was confirmed in vitro and in an in vivo model., Results: TMEM205 expression was 10-20 fold higher in PR compared to PS ovarian cancer cell lines, serum samples, and tissues. Co-localization with CD1B was confirmed by in-situ proximity ligation assay suggesting that TMEM205 may mediate PR via the exosomal pathway. Exosomal secretion was significantly increased 5-10 fold in PR cell lines after treatment with carboplatin compared to PS cell lines. Pre-treatment with L-2663 prior to carboplatin resulted in significantly increased intracellular concentration of fluorescently-labeled cisplatin and decreased exosomal efflux of platinum. Decreased cell survival and tumor growth in vitro and in vivo was observed when PR cells were treated with a combination of L-2663 with carboplatin compared to carboplatin alone., Conclusion: TMEM205 appears to be involved in the development of PR in ovarian cancer through the exosomal efflux of platinum agents. This study provides pre-clinical evidence that TMEM205 could serve as a possible biomarker for PR as well as a therapeutic target in combination with platinum agents., (Published by Elsevier Inc.)

Background: Oncolytic virotherapy (OV) is an immunotherapy that incorporates viral cancer cell lysis with engagement of the recruited immune response against cancer cells. Pediatric solid tumors are challenging targets because they contain both an inert immune environment and a quiet antigenic landscape, making them more resistant to conventional OV approaches. Further complicating this, herpes simplex virus suppresses host gene expression during virotherapy infection., Methods: We therefore developed a multimodal oncolytic herpes simplex virus (oHSV) that expresses ephrin A2 (EphA2), a shared tumor-associated antigen (TAA) expressed by many tumors to improve immune-mediated antitumor activity. We verified the virus genotypically and phenotypically and then tested it in an oHSV-resistant orthotopic model (including immunophenotypic analysis), in flank and in T cell-deficient mouse models. We then assessed the antigen-expressing virus in an unrelated peripheral tumor model that also expresses the shared tumor antigen and evaluated functional T-cell response from the treated mice., Results: Virus-based EphA2 expression induces a robust acquired antitumor immune responses in both an oHSV-resistant murine brain and peripheral tumor model. Our new multimodal oncolytic virus (1) improves survival in viroimmunotherapy resistant tumors, (2) alters both the infiltrating and peripheral T-cell populations capable of suppressing tumor growth on rechallenge, and (3) produces EphA2-specific CD8 effector-like populations., Conclusions: Our results suggest that this flexible viral-based platform enables immune recognition of the shared TAA and improves the immune-therapeutic response, thus making it well suited for low-mutational load tumors., Competing Interests: Competing interests: In the interest of full disclosure, KAC receives licensure payments from Mustang Bio for the C134 virus, but there are no relevant financial conflicts for the technology addressed in this paper., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Here we investigated the impact of oncolytic herpes simplex virus (HSV) treatment on cisplatin sensitivity of platinum-resistant ovarian cancer, and the impact of the combination on immunotherapy., Experimental Design: Therapeutic efficacy of the combination was assessed in platinum-resistant human and murine ovarian cancer peritoneal metastatic mouse models ( n = 9-10/group). RNA sequencing along with flow cytometry of splenocytes from treated mice was employed to examine the effect of antitumor immune response ( n = 3/group). Anti-PD-1 antibody was performed to evaluate impact on checkpoint inhibition in vivo ., Results: Gene Ontology pathway analysis uncovered disruption of cellular extracellular vesicle (EV)-related pathways in infected cells (FDR = 2.97E-57). Mechanistically, we identified reduced expression of transporters expressed on EV implicated in cisplatin efflux. The increased cisplatin retention led to increased cisplatin-DNA adducts, which resulted in micronuclei and the subsequent activation of cGAS-STING pathway with a significant activation of innate immune cells and translated to an increase in antitumor immunity and efficacy. In mice bearing platinum-resistant ovarian cancer, we also observed a feedback induction of PD-L1 on tumor cells, which sensitized combination-treated mice to anti-PD-1 immune checkpoint therapy., Conclusions: To our knowledge, this is the first report to show HSV-induced cisplatin retention in infected cells. The consequential increased damaged DNA was then expelled from cells as micronuclei which resulted in induction of inflammatory responses and education of antitumor immunity. The combination therapy also created an environment that sensitized tumors to immune checkpoint therapy., (©2020 American Association for Cancer Research.)

Background: Hereditary angioedema (HAE) is a rare inherited disorder characterized by sudden and unpredictable appearance of swelling. Surgical procedures, even minor ones, are known to precipitate an attack in these patients. C1 esterase inhibitor (C1-INH) therapy may be effective for short term prophylaxis in such situations. However, there is limited experience with short term prophylaxis in countries where C1-INH therapy is not available., Methods: To report our experience of using short term prophylaxis for a dental procedure, a Cesarean section and a major hip surgery in one patient each with HAE in resource constrained settings., Results: All 3 patients were given FFP before and during the procedure. While the first (a 6-year-old girl) and third patient (a 60-year-old male) were already taking stanozolol and the dose was doubled 5 days before the surgery, the second patient (28-year-old woman) was not taking any prophylaxis and she was initiated on stanozolol on the day of Cesarean section. The first patient was also given additional FFP one day after the dental procedure. After the procedure, the dose of stanozolol was decreased to baseline in patient 1 and 3 while it was discontinued in patient 3. All 3 patients tolerated the procedures well and had no related episodes of angioedema., Conclusions: Dental and other major surgical procedures in patients with HAE are known to precipitate an episode of angioedema. In countries where C1-INH therapy is not available, attenuated androgens and FFP may be used to prevent these episodes., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: Tibial plateau fractures are complex and may result in sub-optimal results despite a timely and excellent reduction. An important cause for this may be the inability to detect and correct sagittal malalignment consequent to a reversal of the posterior tibial slope. We describe here the surgical steps to restore posterior tibial slope in a series of our patients with tibial condyle fractures involving the posterior column fragment using a fixed-angle locking plate., Methods: This was a prospective cohort study of 4 cases who had sustained closed, bicondylar tibial plateau fractures (AO/OTA 41-C3) involving the posterior column fragment and reversed sagittal slope. All patients were operated in a prone position through a posterior approach. The fixation was done with a fixed angle locking plate., Results: The average time taken for fracture union was 12 (range 10-15) weeks. The posterior tibial slope was restored in all the four patients (mean posterior proximal tibial angle = 8.5°, mean medial proximal tibial angle = 88°). There were no procedure-related complications. All patients attained excellent Knee Society Score at one year follow up (mean score = 93)., Conclusion: A posterior approach in the prone position gives direct access to the fracture apex which eases the fracture reduction and fixation to correct the sagittal malalignment in tibial condyle fractures involving the posterior column fragment. We propose this approach as an critical surgical technique which helps in improved outcomes of tibial condylar fractures., Competing Interests: None., (© 2019 Published by Elsevier Ltd.)

This paper pertains to the development & evaluation of a dielectric electroactive polymer-based tactile pressure sensor and its circuitry. The evaluations conceived target the sensor's use case as an in-situ measurement device assessing load conditions imposed by compression garments in either static form or dynamic pulsations. Several testing protocols are described to evaluate and characterize the sensor's effectiveness for static and dynamic response such as repeatability, linearity, dynamic effectiveness, hysteresis effects of the sensor under static conditions, sensitivity to measurement surface curvature and temperature and humidity effects. Compared to pneumatic sensors in similar physiological applications, this sensor presents several significant advantages including better spatial resolution, compact packaging, manufacturability for smaller footprints and overall simplicity for use in array configurations. The sampling rates and sensitivity are also less prone to variability compared to pneumatic pressure sensors. The presented sensor has a high sampling rate of 285 Hz that can further assist with the physiological applications targeted for improved cardiac performance. An average error of ± 5.0 mmHg with a frequency of 1-2 Hz over a range of 0 to 120 mmHg was achieved when tested cyclically.

Hypoxia-mediated tumor progression, metastasis, and drug resistance are major clinical challenges in ovarian cancer. Exosomes released in the hypoxic tumor microenvironment may contribute to these challenges by transferring signaling proteins between cancer cells and normal cells. We observed that ovarian cancer cells exposed to hypoxia significantly increased their exosome release by upregulating Rab27a, downregulating Rab7, LAMP1/2, NEU-1, and also by promoting a more secretory lysosomal phenotype. STAT3 knockdown in ovarian cancer cells reduced exosome release by altering the Rab family proteins Rab7 and Rab27a under hypoxic conditions. We also found that exosomes from patient-derived ascites ovarian cancer cell lines cultured under hypoxic conditions carried more potent oncogenic proteins-STAT3 and FAS that are capable of significantly increasing cell migration/invasion and chemo-resistance in vitro and tumor progression/metastasis in vivo. Hypoxic ovarian cancer cells derived exosomes (HEx) are proficient in re-programming the immortalized fallopian tube secretory epithelial cells (FT) to become pro-tumorigenic in mouse fallopian tubes. In addition, cisplatin efflux via exosomes was significantly increased in ovarian cancer cells under hypoxic conditions. Co-culture of HEx with tumor cells led to significantly decreased dsDNA damage and increased cell survival in response to cisplatin treatment. Blocking exosome release by known inhibitor Amiloride or STAT3 inhibitor and treating with cisplatin resulted in a significant increase in apoptosis, decreased colony formation, and proliferation. Our results demonstrate that HEx are more potent in augmenting metastasis/chemotherapy resistance in ovarian cancer and may serve as a novel mechanism for tumor metastasis, chemo-resistance, and a point of intervention for improving clinical outcomes.

The initial molecular events that lead to malignant transformation of the fimbria of the fallopian tube (FT) through high-grade serous ovarian carcinoma (HGSC) remain poorly understood. In this study, we report that increased expression of signal transducer and activator of transcription 3 ( pSTAT3 Tyr705 ) and suppression or loss of protein inhibitor of activated STAT3 ( PIAS3 ) in FT likely drive HGSC. We evaluated human tissues-benign normal FT, tubal-peritoneal junction (TPJ), p53 signature FT tissue, tubal intraepithelial lesion in transition (TILT), serous tubal intraepithelial carcinoma (STIC) without ovarian cancer, and HGSC for expression of STAT3/PIAS3 (compared with their known TP53 signature) and their target proliferation genes. We observed constitutive activation of STAT3 and low levels or loss of PIAS3 in the TPJ, p53 signature, TILT, and STIC through advanced stage IV (HGSC) tissues. Elevated expression of pSTAT3 Tyr705 and decreased levels of PIAS3 appeared as early as TPJ and the trend continued until very advanced stage HGSC (compared with high PIAS3 and low pSTAT3 expression in normal benign FT). Exogenous expression of STAT3 in FT cells mediated translocation of pSTAT3 and c-Myc into the nucleus. In vivo experiments demonstrated that overexpression of STAT3 in FT secretory epithelial cells promoted tumor progression and metastasis, mimicking the clinical disease observed in patients with HGSC. Thus, we conclude that the STAT3 pathway plays a role in the development and progression of HGSC from its earliest premalignant states. Significance: Concomitant gain of pSTAT3 Tyr705 and loss of PIAS3 appear critical for initiation and development of high-grade serous carcinoma. Cancer Res; 78(7); 1739-50. ©2018 AACR ., (©2018 American Association for Cancer Research.)