bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary lymphoma of the female genital tract masquerading as gynecological malignancy
Authors: Shi Suhua , Li Wuan , Ni Guantai , Ding Jin , Liu Yinhua , Wu Haixing , Zhang Zhen , Ding Zhimin
Published: April 2024

Background

Primary lymphoma of the female genital tract (PLFGT) is a rare malignant tumor in the female reproductive system, with a low incidence and few clinical reports. The aim of this study is to report our institutional experience with this rare malignancy and emphasize the need for increasing the awareness about PLFGT presenting with gynecologic symptoms.

Methods

The medical records of patients diagnosed with PLFGT from March 2014 to November 2022 in the First Affiliated Hospital of Wannan Medical College were reviewed. Histological classification and staging were based on the World Health Organization and Ann Arbor systems, respectively.

Results

There were 13 patients with diagnosis of PLFGT and the median length of follow-up was 31 months (0-102 months). The main clinical symptoms included postmenopausal vaginal bleeding, pelvic mass and abdominal pain. Serum LDH increased in 10 patients and serum CA125 elevated in 2 patients. The tumor of ovarian or uterine presented as solid masses in CT or MRI, and ascites was rare. The histological subtypes were diffuse large B-cell (n = 12) and follicular (n = 1) lymphoma. Tumors were located in ovary (n = 8), uterus (n = 3), and cervix (n = 2). According to the Ann Arbor staging system, 6 cases were classified as stage II and 7 cases were classified as stage IV, respectively. A total of 10 patients underwent surgery. Combination chemotherapy was used in 10 patients. Eight patients had tumor-free survival, 1 patient had recurrent disease, 3 patients died and 1 patient lost to follow-up. The median survival time was 32 months (1-102 months).

Conclusion

PLFGT usually presents as gynecological symptoms and solid masses in pelvis. Surgery or biopsy was the way to obtain the pathologic diagnosis, and combination chemotherapy is the efficient method for PLFGT. Making an accurate preoperative diagnosis is of paramount importance to avoid radical gynecologic surgery.
Implementation of the Dementia Isolation Toolkit in long-term care improves awareness but does not reduce moral distress amongst healthcare providers
Authors: Levy Anne Marie , Grigorovich Alisa , McMurray Josephine , Quirt Hannah , Ranft Kaitlyn , Engell Katia , Stewart Steven , Astell Arlene , Kokorelias Kristina , Schon Denise , Rogrigues Kevin , Tsokas Mario , Flint Alastair J. , Iaboni Andrea
Published: April 2024

Background

Healthcare providers may experience moral distress when they are unable to take the ethically or morally appropriate action due to real or perceived constraints in delivering care, and this psychological stressor can negatively impact their mental health, leading to burnout and compassion fatigue. This study describes healthcare providers experiences of moral distress working in long-term care settings during the COVID-19 pandemic and measures self-reported levels of moral distress pre- and post-implementation of the Dementia Isolation Toolkit (DIT), a person-centred care intervention designed for use by healthcare providers to alleviate moral distress.

Methods

Subjective levels of moral distress amongst providers (e.g., managerial, administrative, and front-line employees) working in three long-term care homes was measured pre- and post-implementation of the DIT using the Moral Distress in Dementia Care Survey and semi-structured interviews. Interviews explored participants’ experiences of moral distress in the workplace and the perceived impact of the intervention on moral distress.

Results

A total of 23 providers between the three long-term care homes participated. Following implementation of the DIT, subjective levels of moral distress measured by the survey did not change. When interviewed, participants reported frequent experiences of moral distress from implementing public health directives, staff shortages, and professional burnout that remained unchanged following implementation. However, in the post-implementation interviews, participants who used the DIT reported improved self-awareness of moral distress and reductions in the experience of moral distress. Participants related this to feeling that the quality of resident care was improved by integrating principals of person-centered care and information gathered from the DIT.

Conclusions

This study highlights the prevalence and exacerbation of moral distress amongst providers during the pandemic and the myriad of systemic factors that contribute to experiences of moral distress in long-term care settings. We report divergent findings with no quantitative improvement in moral distress post-intervention, but evidence from interviews that the DIT may ease some sources of moral distress and improve the perceived quality of care delivered. This study demonstrates that an intervention to support person-centred isolation care in this setting had limited impact on overall moral distress during the COVID-19 pandemic.
The endothelium: gatekeeper to lung ischemia-reperfusion injury
Authors: Ta Huy Q. , Kuppusamy Maniselvan , Sonkusare Swapnil K. , Roeser Mark E. , Laubach Victor E.
Published: April 2024

The success of lung transplantation is limited by the high rate of primary graft dysfunction due to ischemia-reperfusion injury (IRI). Lung IRI is characterized by a robust inflammatory response, lung dysfunction, endothelial barrier disruption, oxidative stress, vascular permeability, edema, and neutrophil infiltration. These events are dependent on the health of the endothelium, which is a primary target of IRI that results in pulmonary endothelial barrier dysfunction. Over the past 10 years, research has focused more on the endothelium, which is beginning to unravel the multi-factorial pathogenesis and immunologic mechanisms underlying IRI. Many important proteins, receptors, and signaling pathways that are involved in the pathogenesis of endothelial dysfunction after IR are starting to be identified and targeted as prospective therapies for lung IRI. In this review, we highlight the more significant mediators of IRI-induced endothelial dysfunction discovered over the past decade including the extracellular glycocalyx, endothelial ion channels, purinergic receptors, kinases, and integrins. While there are no definitive clinical therapies currently available to prevent lung IRI, we will discuss potential clinical strategies for targeting the endothelium for the treatment or prevention of IRI. The accruing evidence on the essential role the endothelium plays in lung IRI suggests that promising endothelial-directed treatments may be approaching the clinic soon. The application of therapies targeting the pulmonary endothelium may help to halt this rapid and potentially fatal injury.
Prevalence of overweight and obesity among adolescents living with HIV after dolutegravir - based antiretroviral therapy start in Kampala, Uganda
Authors: Nakatudde Irene , Katana Elizabeth , Agnes Odongpiny Eva Laker , Nalugga Esther Alice , Castelnuovo Barbara , Fowler Mary Glenn , Musoke Philippa
Published: April 2024

Background

Dolutegravir (DTG)-based antiretroviral therapy (ART) is currently the preferred first-line treatment for persons living with HIV (PLHIV) including children and adolescents in many low- and middle-income countries including Uganda. However, there are concerns about excessive weight gain associated with DTG especially in adults. There remains paucity of current information on weight-related outcomes among adolescents on DTG. We determined the prevalence of excessive weight gain and associated factors among adolescents living with HIV (ALHIV) receiving DTG-based ART in Kampala, Uganda.

Methods

Cross-sectional study involving ALHIV aged 10–19 years on DTG-based ART for at least one year were recruited from public health facilities in Kampala between February and May 2022. Excessive weight gain was defined as becoming overweight or obese per body mass index (BMI) norms while on DTG-based ART for at least one year. Demographic, clinical and laboratory data were collected using interviewer-administered questionnaires and data extracted from medical records. At enrolment, blood pressure and anthropometry were measured and blood was drawn for blood glucose and lipid profile. Data was summarised using descriptive statistics and logistic regression was performed to determine the associated factors.

Results

We enrolled 165 ALHIV with a median age of 14 years (IQR 12–16). Eighty (48.5%) were female. The median duration on ART and DTG was 8 years (IQR 7–11) and 2 years (IQR 1–3) respectively. At DTG initiation, the majority of participants (152/165, 92.1%) were ART-experienced, and had normal BMI (160/165, 97%). Overall, 12/165 (7.3%) adolescents (95% CI: 4.2–12.4) had excessive weight gain. No factors were significantly associated with excessive weight gain after DTG start in ALHIV. However, all ALHIV with excessive weight gain were females.

Conclusion

Our study found a prevalence of 7.3% of overweight and obesity in ALHIV after initiating DTG. We did not find any factor significantly associated with excessive weight gain in ALHIV on DTG. Nonetheless, we recommend ongoing routine monitoring of anthropometry and metabolic markers in ALHIV as DTG use increases globally, to determine the exact magnitude of excessive weight gain and to identify those at risk of becoming overweight or obese while taking the medication.
The efficacy of minimally invasive coronary artery bypass grafting (mics cabg) for patients with coronary artery diseases and diabetes: a single center retrospective study
Authors: Guangxin Zhao , Liqun Chi , Lin Liang , Jiaji Liu , Xiaolong Ma , Yuxiao Zhang , Qiuyue Huang , Qingyu Kong
Published: April 2024

Background

conventional coronary artery bypass grafting (CCABG) tends to cause severe complications in patients with comorbid Coronary Artery Diseases (CAD) and diabetes. On the other hand, the Minimally Invasive Cardiac Surgery Coronary Artery Bypass Grafting (MICS CABG) via transthoracic incision is associated with rapid recovery and reduced complications. Adding to the limited literature, this study compares CCABG and MICS CABG in terms of efficacy and safety.

Methods

Herein, 104 CCABG and MICS CABG cases (52 cases each) were included. The patients were recruited from the Minimally Invasive Cardiac Surgery Center, Anzhen Hospital, between January 2017 and December 2021 and were selected based on the Propensity Score Matching (PSM) model. The key outcomes included All-cause Death, Myocardial Infarction (MI), Cerebrovascular Events, revascularization, Adverse Wound Healing Events and one-year patency of the graft by coronary CTA.

Results

Compared to CCABG, MICS CABG had longer surgical durations [4.25 (1.50) h vs.4.00 (1.13) h, P = 0.028], but showed a reduced intraoperative blood loss [600.00 (400.00) mL vs.700.00 (300.00) mL, P  = 0.032] and a lower secondary incision debridement and suturing rate (5.8% vs.19.2%, P = 0.038). In follow up, no statistically significant differences were found between the two groups in the cumulative Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs) incidence (7.7% vs. 5.9%), all-cause mortality (0 vs. 0), MI incidence (1.9% vs. 2.0%), cerebral apoplexy incidence (5.8% vs. 3.9%), and repeated revascularization incidence (0 vs. 0) (P > 0.05). Additionally, coronary CTA results revealed that the two groups’ one-year graft patency (94.2% vs. 90.2%, P = 0.761) showed no statistically significant difference.

Conclusion

In patients with comorbid CAD and diabetes, MICS CABG and CCABG had comparable revascularization performances. Moreover, MICS CABG can effectively reduce, if not prevent, poor clinical outcomes/complications, including incision healing, sternal infection and prolonged length of stay in diabetes patients.
Adaptive space-time model order reduction with dual-weighted residual (MORe DWR) error control for poroelasticity
Authors: Fischer Hendrik , Roth Julian , Chamoin Ludovic , Fau Amélie , Wheeler Mary , Wick Thomas
Published: April 2024

In this work, the space-time MORe DWR (Model Order Reduction with Dual-Weighted Residual error estimates) framework is extended and further developed for single-phase flow problems in porous media. Specifically, our problem statement is the Biot system which consists of vector-valued displacements (geomechanics) coupled to a Darcy flow pressure equation. The MORe DWR method introduces a goal-oriented adaptive incremental proper orthogonal decomposition (POD) based-reduced-order model (ROM). The error in the reduced goal functional is estimated during the simulation, and the POD basis is enriched on-the-fly if the estimate exceeds a given threshold. This results in a reduction of the total number of full-order-model solves for the simulation of the porous medium, a robust estimation of the quantity of interest and well-suited reduced bases for the problem at hand. We apply a space-time Galerkin discretization with Taylor-Hood elements in space and a discontinuous Galerkin method with piecewise constant functions in time. The latter is well-known to be similar to the backward Euler scheme. We demonstrate the efficiency of our method on the well-known two-dimensional Mandel benchmark and a three-dimensional footing problem.
Dissociation of prepotent response inhibition and interference control in problematic internet use: evidence from the Go/No-Go and Flanker tasks
Authors: Zhang Shao-Shuai , Zhong Yu-qing , Li Xu , Peng Ming
Published: April 2024

Background

Problematic Internet Use (PIU), characterized by failures to control the overuse of internet, is associated with a range of functional impairments. However, there is limited research on the specific impact of PIU on inhibitory control functions, particularly in terms of differentiating between prepotent response inhibition and interference control. Therefore, the main objective of this study is to investigate these two components of inhibitory control in individuals with PIU.

Methods

Thirty participants who met the PIU criteria and 30 control participants were included in the present study. All participants completed the Go/No-Go and Flanker tasks, in which internet-related images and words were used as task stimuli.

Results

In the Go/No-Go task, all participants exhibited poorer performance in inhibiting internet-related stimuli compared to internet-unrelated stimuli, during the No-Go trials. In the Flanker task, results revealed a three-way interaction of Group, Stimulus type and Congruency. Specifically, in the incongruent condition, participants with PIU exhibited slower responses for internet-unrelated targets compared to internet-related targets, whereas no similar effect was observed among individuals with low internet use.

Conclusions

The findings suggest that difficulties in controlling the interference effect of internet-related information represent a key dysfunction in inhibitory control of PIU.
An improved deep hashing model for image retrieval with binary code similarities
Authors: Liu Huawen , Wu Zongda , Yin Minghao , Yu Donghua , Zhu Xinzhong , Lou Jungang
Published: April 2024

The exponential growth of data raises an unprecedented challenge in data analysis: how to retrieve interesting information from such large-scale data. Hash learning is a promising solution to address this challenge, because it may bring many potential advantages, such as extremely high efficiency and low storage cost, after projecting high-dimensional data to compact binary codes. However, traditional hash learning algorithms often suffer from the problem of semantic inconsistency, where images with similar semantic features may have different binary codes. In this paper, we propose a novel end-to-end deep hashing method based on the similarities of binary codes, dubbed CSDH (Code Similarity-based Deep Hashing), for image retrieval. Specifically, it extracts deep features from images to capture semantic information using a pre-trained deep convolutional neural network. Additionally, a hidden and fully connected layer is attached at the end of the deep network to derive hash bits by virtue of an activation function. To preserve the semantic consistency of images, a loss function has been introduced. It takes the label similarities, as well as the Hamming embedding distances, into consideration. By doing so, CSDH can learn more compact and powerful hash codes, which not only can preserve semantic similarity but also have small Hamming distances between similar images. To verify the effectiveness of CSDH, we evaluate CSDH on two public benchmark image collections, i.e., CIFAR-10 and NUS-WIDE, with five classic shallow hashing models and six popular deep hashing ones. The experimental results show that CSDH can achieve competitive performance to the popular deep hashing algorithms.
Microneedle-mediated nanomedicine to enhance therapeutic and diagnostic efficacy
Authors: Zuo Yuyang , Sun Rujie , Del Piccolo Nuala , Stevens Molly M.
Published: April 2024

Nanomedicine has been extensively explored for therapeutic and diagnostic applications in recent years, owing to its numerous advantages such as controlled release, targeted delivery, and efficient protection of encapsulated agents. Integration of microneedle technologies with nanomedicine has the potential to address current limitations in nanomedicine for drug delivery including relatively low therapeutic efficacy and poor patient compliance and enable theragnostic uses. In this Review, we first summarize representative types of nanomedicine and describe their broad applications. We then outline the current challenges faced by nanomedicine, with a focus on issues related to physical barriers, biological barriers, and patient compliance. Next, we provide an overview of microneedle systems, including their definition, manufacturing strategies, drug release mechanisms, and current advantages and challenges. We also discuss the use of microneedle-mediated nanomedicine systems for therapeutic and diagnostic applications. Finally, we provide a perspective on the current status and future prospects for microneedle-mediated nanomedicine for biomedical applications.
A straightforward chemobiocatalytic route for one-pot valorization of glucose into 2,5-bis(hydroxymethyl)furan
Authors: Liao Xuan-Ping , Wu Qian , Zong Min-Hua , Li Ning
Published: April 2024

Direct conversion of inexpensive biomass into value-added chemicals via furanic platform molecules is highly attractive. In this work, we present a straightforward chemobiocatalytic route for glucose valorization into 2,5-bis(hydroxymethyl)furan (BHMF) in one pot, with no purification of the intermediate 5-hydroxymethylfurfural (HMF). Six candidate alcohol dehydrogenase (ADH) genes were located from Meyerozyma guilliermondii SC1103, based on comparative transcriptome analysis and real-time quantitative polymerase chain reaction. An ADH (MgADH1) was identified upon evaluation of catalytic performances of recombinant Saccharomyces cerevisiae harboring candidate ADHs in HMF reduction. Soluble expression of the enzyme in S. cerevisiae was greatly enhanced by its codon optimization, leading to improved HMF tolerance (up to 400 mM). In a fed-batch process, the desired product of approximately 473 mM (60.5 g/L) was produced within 30 h by recombinant S. cerevisiae_MgADH1. A chemobiocatalytic route toward BHMF was constructed by merging CaCl2-mediated isomerization and dehydration with biocatalytic reduction with an overall yield of approximately 42%, starting from glucose. This work may pave the way for green manufacture of valuable biobased chemicals.
Cellular therapeutics and immunotherapies in wound healing – on the pulse of time?
Authors: Huelsboemer Lioba , Knoedler Leonard , Kochen Alejandro , Yu Catherine T. , Hosseini Helia , Hollmann Katharina S. , Choi Ashley E. , Stögner Viola A. , Knoedler Samuel , Hsia Henry C. , Pomahac Bohdan , Kauke-Navarro Martin
Published: April 2024

Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring significant human and financial resources. Chronic wounds arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, and genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization and the formation of biofilms. Infection, consequently, perpetuates a chronic inflammatory microenvironment, preventing the progression and completion of normal wound healing. The current standard of care (SOC) for chronic wounds involves surgical debridement along with localized wound irrigation, which requires inpatient care under general anesthesia. This could be followed by, if necessary, defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft, local, or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored. To promote physiological wound healing, a variety of approaches have been subjected to translational research. Beyond conventional wound healing drugs and devices that currently supplement treatments, cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell- or molecule-specific wound healing properties. However, in contrast to the clinical omnipresence of chronic wound healing disorders, there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds. This review provides a comprehensive exploration of current therapies, experimental approaches, and translational studies, offering insights into their efficacy and limitations. Ultimately, we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.
A case of laparoscopic lymphadenectomy for adenocarcinoma of unknown primary incidentally detected as a solitary enlarged lymph node along the common hepatic artery
Authors: Morimoto Tomonori , Hisamori Shigeo , Kinoshita Hiromitsu , Yamada Yosuke , Teramoto Yuki , Sakamoto Takashi , Kasahara Keiko , Okumura Shintaro , Nishigori Tatsuto , Tsunoda Shigeru , Obama Kazutaka
Published: April 2024

Background

Even in cancer of unknown primary (CUP), which is rare clinical condition, solitary anterosuperior lymph node (LN) along the common hepatic artery (No.8a LN) enlargement diagnosed as metastatic adenocarcinoma has never been reported.

Case presentation

A 68-year-old Japanese male, with a history of early gastric cancer that had been completely treated by endoscopic submucosal dissection 26 years ago, was detected a single enlarged nodule along the common hepatic artery, No.8a LN, incidentally by computed tomography performed for monitoring of interstitial pneumonia. Endoscopic ultra-sound-guided fine needle aspiration revealed that this nodule was adenocarcinoma suggestive of metastasis, but other imaging studies, including upper and lower gastrointestinal endoscopy, positron emission tomography, and ultrasonography did not detect any primary cancer. We have finally diagnosed as the LN metastasis of CUP and performed laparoscopic lymphadenectomy for this tumor. The tumor was approximately 5 cm in size, was in close proximity to the pancreas, and involved part of the right gastric artery and vein. LNs in the No.5 and No.8a areas, including this tumor, were dissected laparoscopically, and radical resection was achieved. The patient had no postoperative complication and was discharged on postoperative day 10. Immunohistopathological findings revealed that the tumor was poorly differentiated adenocarcinoma, and different from the histology of gastric cancer resected 26 years ago, although the tumor was suggestive of gastrointestinal origin. Imaging studies performed 2 and 6 months after discharge also did not reveal a primary site.

Conclusion

We reported a case of solitary No.8a LN adenocarcinoma of CUP. For diagnostic and therapeutic purposes, radical resection is recommended for single enlarged intra-abdominal LN of CUP.
Wallace’s line structures seagrass microbiota and is a potential barrier to the dispersal of marine bacteria
Authors: Wainwright Benjamin J. , Leon Josh , Vilela Ernie , Hickman K. J. E. , Caldwell Jensen , Aimone Behlee , Bischoff Porter , Ohran Marissa , Morelli Magnolia W. , Arlyza Irma S. , Marwayana Onny N. , Zahn Geoffrey
Published: April 2024

Background

The processes that shape microbial biogeography are not well understood, and concepts that apply to macroorganisms, like dispersal barriers, may not affect microorganisms in the same predictable ways. To better understand how known macro-scale biogeographic processes can be applied at micro-scales,we examined seagrass associated microbiota on either side of Wallace’s line to determine the influence of this cryptic dispersal boundary on the community structure of microorganisms. Communities were examined from twelve locations throughout Indonesia on either side of this theoretical line.

Results

We found significant differences in microbial community structure on either side of this boundary (R2 = 0.09;P = 0.001), and identified seven microbial genera as differentially abundant on either side of the line, six of these were more abundant in the West, with the other more strongly associated with the East. Genera found to be differentially abundant had significantly smaller minimum cell dimensions (GLM: t923 = 59.50,P < 0.001) than the overall community.

Conclusion

Despite the assumed excellent dispersal ability of microbes, we were able to detect significant differences in community structure on either side of this cryptic biogeographic boundary. Samples from the two closest islands on opposite sides of the line, Bali and Komodo, were more different from each other than either was to its most distant island on the same side. We suggest that limited dispersal across this barrier coupled with habitat differences are primarily responsible for the patterns observed. The cryptic processes that drive macroorganism community divergence across this region may also play a role in the bigeographic patterns of microbiota.
Recommendations for optimising pilot and feasibility work in surgery
Authors: Fairhurst K. , Potter S. , Blazeby J. M. , Avery K. N. L.
Published: April 2024

Background

Surgical trials are recognised as inherently challenging. Pilot and feasibility studies (PAFS) are increasingly acknowledged as a key method to optimise the design and conduct of randomised trials but remain limited in surgery. We used a mixed methods approach to develop recommendations for how surgical PAFS could be optimised.

Methods

The findings from a quantitative analysis of funded surgical PAFS over a 10-year period and in-depth qualitative interviews with surgeons, methodologists and funders were triangulated and synthesised with available methodological guidance on PAFS.

Results

The synthesis informed the development of an explanatory model describing root causes and compounding challenges that contribute to how and why surgical PAFS is not currently optimised. The four root causes identified include issues relating to (i) understanding the full scope of PAFS; (ii) design and conduct of PAFS; (iii) reporting of PAFS; and (iv) lack of appreciation of the value of PAFS by all stakeholder groups. Compounding challenges relate to both cultural issues and access to and interpretation of available methodological PAFS guidance. The study findings and explanatory model were used to inform the development of a practical guidance tool for surgeons and study teams to improve research practice.

Conclusions

Optimisation of PAFS in surgery requires a cultural shift in research practice amongst funders, academic institutions, regulatory bodies and journal editors, as well as amongst surgeons. Our ‘Top Tips’ guidance tool offers an accessible framework for surgeons designing PAFS. Adoption and utilisation of these recommendations will optimise surgical PAFS, facilitating successful and efficient future surgical trials.
How can we support research participants who stop taking part? Communications guidance developed through public-researcher collaboration
Authors: Cragg William J. , Bishop Liam , Gilberts Rachael , Gregg Michael , Lowdon Terry , Mancini Mary , Martins de Barros Clara , Wheatstone Pete
Published: April 2024

Background

Research study participants can stop taking part early, in various circumstances. Sometimes this experience can be stressful. Providing participants with the information they want or need when they stop could improve participants’ experiences, and may benefit individual studies’ objectives and research in general. A group of public contributors and researchers at the Clinical Trials Research Unit, University of Leeds, aimed to develop a communication template and researcher guidance. This would address how to provide information sensitively around the time when participants stop or significantly reduce their level of participation.

Methods

The project lead used scoping review methods to identify relevant prior evidence and derive a list of potential information topics to communicate to participants who stop taking part. The topic list was reviewed by research professionals and public contributors before finalisation. Further public contributors were identified from a range of networks. The contributors formed a ‘development group’, to work on the detail of the planned resources, and a larger ‘review group’ to review the draft output before finalisation. The involvement was planned so that the development group could shape the direction and pace of the work.

Results

The literature review identified 413 relevant reports, resulting in 94 information topics. The review suggested that this issue has not been well explored previously. Some evidence suggested early-stopping participants are sometimes excluded from important communications (such as study results) without clear justification. The development group agreed early to focus on guidance with reusable examples rather than a template. We took time to explore different perspectives and made decisions by informal consensus. Review group feedback was broadly positive but highlighted the need to improve resource navigability, leading to its final online form.

Conclusions

We co-developed a resource to provide support to research participants who stop taking part. A strength of this work is that several of the public contributors have direct lived experience of stopping research participation. We encourage others to review the resource and consider how they support these participants in their studies. Our work highlights the value of researchers and participants working together, including on complex and ethically challenging topics.
Radiolabeled 15-mer peptide internalization is mediated by megalin (LRP2 receptor) in a CRISPR/Cas9-based LRP2 knockout human kidney cell model
Authors: Durinova Anna , Smutna Lucie , Barta Pavel , Kamaraj Rajamanikkam , Smutny Tomas , Schmierer Bernhard , Pavek Petr , Trejtnar Frantisek
Published: April 2024

Background

Megalin (LRP2 receptor) mediates the endocytosis of radiolabeled peptides into proximal tubular kidney cells, which may cause nephrotoxicity due to the accumulation of a radioactive tracer. The study aimed to develop a cellular model of human kidney HK2 cells with LRP2 knockout (KO) using CRISPR/Cas9 technique. This model was employed for the determination of the megalin-mediated accumulation of 68Ga- and 99mTc-labeled 15-mer peptide developed to target the vascular endothelial growth factor (VEGF) receptor in oncology radiodiagnostics.

Results

The gene editing in the LRP2 KO model was verified by testing two well-known megalin ligands when higher viability of KO cells was observed after gentamicin treatment at cytotoxic concentrations and lower FITC-albumin internalization by the KO cells was detected in accumulation studies. Fluorescent-activated cell sorting was used to separate genetically modified LRP2 KO cell subpopulations. Moreover, flow cytometry with a specific antibody against megalin confirmed LRP2 knockout. The verified KO model identified both 68Ga- and 99mTc-radiolabeled 15-mer peptides as megalin ligands in accumulation studies. We found that both radiolabeled 15-mers enter LRP2 KO HK2 cells to a lesser extent compared to parent cells. Differences in megalin-mediated cellular uptake depending on the radiolabeling were not observed. Using biomolecular docking, the interaction site of the 15-mer with megalin was also described.

Conclusion

The CRISPR/Cas9 knockout of LRP2 in human kidney HK2 cells is an effective approach for the determination of radiopeptide internalization mediated by megalin. This in vitro method provided direct molecular evidence for the cellular uptake of radiolabeled anti-VEGFR 15-mer peptides via megalin.

Graphical abstract
Unusual coexistence of restrictive heart disease and Kallmann syndrome: a case report
Authors: Bennani Ghali , Zahri Soukaina , Khaldi Mohamed , Benouna Ghali , Drighil Abdenasser , Habbal Rachida
Published: April 2024

Background

Kallmann–Morsier syndrome is a rare disease characterized by the association of congenital gonadotropic deficiency and anosmia or hyposmia. The cardiac manifestations associated with this syndrome are little known. Through this case, we will characterize the cardiac involvement of this disease in the light of what is already described in the literature.

Case presentation

We report the case of a young patient who presented with a picture of cardiac decompensation revealing restrictive heart disease. In her exploration, she was found to have primary amenorrhea, leading to the diagnosis of Kallmann syndrome. Medical treatment was optimized for the management of her cardiac decompensation as well as hormonal replacement treatment for her delayed puberty and growth.

Conclusions

Cardiac manifestations in Kallmann–Morsier syndrome are few reported in the literature, and restrictive heart disease is uncommon with no cases report till now. This association suggests a possible common genetic origin that should be explored in the future.
Transition to suicide ideation and attempt among emergency room patients
Authors: Yurdadön Claudio , Bruffaerts Ronny , Sabbe Marc , Demyttenaere Koen , Peeters Elke , Gericke Franco , Voorspoels Wouter
Published: April 2024

Background

Suicidal thoughts and behaviours (STB) represent a persistent and serious public health problem, and suicide is among the leading causes of death worldwide. We focus on predictors of transition rates and time courses through the STB spectrum among psychiatric emergency room (PER) patients.

Aims

We aimed to investigate (a) whether currently suicidal patients had prior referrals to the PER, (b) for which reason they were previously referred to the PER and (c) the timing of this referral.

Method

We performed a retrospective study spanning 20 years with 24 815 PER referrals. Descriptive statistics of patients’ sociodemographic and clinical characteristics are provided and expressed as weighted proportions and means. Logistic regression was used to identify risk profiles of patients who had a higher chance of being referred for reasons of STB given their PER history. Multiple imputation and data weighting techniques were implemented.

Results

STB among PER patients was persistent and led to repeated referrals (up to five times more likely), often within a short period (18% <1 month). Those previously referred for ideation/plan had 66% higher risk of making the transition to suicide attempt, with 25% making this transition within a month after previous referral. This is similar to the transition from depressed mood to suicide ideation/plan.

Conclusions

STBs in PER patients are persistent and lead to repeated referrals, often within a short period, including transitions to more severe forms of STB.
Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer–Associated Germline Pathogenic Variants in Mexico
Authors: Mesa-Chavez Fernanda , Chavarri-Guerra Yanin , Aguilar-y-Mendez Dione , Becerril-Gaitan Andrea , Vaca-Cartagena Bryan F. , Carrillo-Bedoya Araceli , Santiesteban-González Salvador , Aranda-Gutierrez Alejandro , Rodríguez-Faure Andrés , Obregon-Leal Daniela , Quintero-Beuló Gregorio , Rodriguez-Olivares Jose L. , Miaja Melina , Weitzel Jeffrey N. , Villarreal-Garza Cynthia
Published: April 2024

PURPOSE

Genetic cancer risk assessment (GCRA) provides pathogenic variant (PV) carriers with the invaluable opportunity to undertake timely cancer risk-reducing (RR) measures and initiate cascade testing (CT). This study describes the uptake of these strategies and the related barriers among breast cancer–associated germline PV carriers in Mexico.

METHODS

Carriers who were at least 6 months after disclosure of genetic test results at two GCRA referral centers were invited to answer a survey assessing sociodemographic characteristics, awareness of their carrier status and its implications, uptake of RR measures according to international guidelines by PV, CT initiation, and associated challenges.

RESULTS

Of the eligible carriers, 246/384 (64%) answered the survey (median age: 44 years). Most were female (88%), married/in domestic partnership (66%), and had personal breast/ovarian cancer history (61%). PVs included BRCA1/ 2 (75%), CHEK2 (10%), PALB2 (5%), ATM (5%), NF1 (2%), RAD51C (2%), PTEN (1%), and TP53 (1%). Most (87%) participants were aware of their carrier status. When recommended, 37% underwent RR bilateral mastectomy, 48% RR oophorectomy, 70% annual mammogram, and 20% breast magnetic resonance imaging. Challenges hindering the uptake of RR measures included financial limitations (67%), lack of recommendation by their physician (35%), and fear (24%). Nearly all (98%) claimed sharing their results with their relatives. CT was initiated in 63% of families and was associated with carriers being married/in domestic partnership ( P = .04) and believing GCRA was useful ( P < .001).

CONCLUSION

Despite the resource-constrained setting, relevant rates of RR measures and CT were observed. Targeted interventions to reduce out-of-pocket expenses and improve patient-physician communication and patients' understanding on carrier status are warranted to enhance the overall benefit of GCRA and ultimately improve the provision of patient-centered care to both carriers and their at-risk relatives.
Randomized Phase II Study of Gemcitabine With or Without ATR Inhibitor Berzosertib in Platinum-Resistant Ovarian Cancer: Final Overall Survival and Biomarker Analyses
Authors: Konstantinopoulos Panagiotis A. , Cheng Su-Chun , Lee Elizabeth K. , da Costa Alexandre André B.A. , Gulhan Doga , Wahner Hendrickson Andrea E. , Kochupurakkal Bose , Kolin David L. , Kohn Elise C. , Liu Joyce F. , Penson Richard T. , Stover Elizabeth H. , Curtis Jennifer , Sawyer Hannah , Polak Madeline , Chowdhury Dipanjan , D'Andrea Alan D. , Färkkilä Anniina , Shapiro Geoffrey I. , Matulonis Ursula A.
Published: April 2024

PURPOSE

The multicenter, open-label, randomized phase 2 NCI-9944 study ( NCT02595892 ) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone (hazard ratio [HR]=0.57, one-sided log-rank P = .044, which met the one-sided significance level of 0.1 used for sample size calculation).

METHODS

We report here the final overall survival (OS) analysis and biomarker correlations (ATM expression by immunohistochemistry, mutational signature 3 and a genomic biomarker of replication stress) along with post-hoc exploratory analyses to adjust for crossover from gemcitabine to gemcitabine/berzosertib.

RESULTS

At the data cutoff of January 27, 2023 (>30 months of additional follow-up from the primary analysis), median OS was 59.4 weeks with gemcitabine/berzosertib versus 43.0 weeks with gemcitabine alone (HR 0.79, 90% CI 0.52 to 1.2, one-sided log-rank P = .18). An OS benefit with addition of berzosertib to gemcitabine was suggested in patients stratified into the platinum-free interval ≤3 months (N = 26) subgroup (HR, 0.48, 90% CI 0.22 to 1.01, one-sided log-rank P =.04) and in patients with ATM-negative/low (N = 24) tumors (HR, 0.50, 90% CI 0.23 to 1.08, one-sided log-rank P = .06).

CONCLUSION

The results of this follow-up analysis continue to support the promise of combined gemcitabine/ATRi therapy in platinum resistant ovarian cancer, an active area of investigation with several ongoing clinical trials.
Apartheid Remains
Authors: Chari Sharad
Published: April 2024

In Apartheid Remains, Sharad Chari explores how people handle the remains of segregation and apartheid in South Africa as witnessed through portals in an industrial-residential landscape in the Indian Ocean city of Durban. Through long-term historical and ethnographic research, Chari portrays South Africa's twentieth century as a palimpsest that conserves the remains of multiple pasts, including attempts by the racial state to remake territory and personhood, while instead deepening spatial contradictions and struggles. When South Durban's denizens collectively mobilized in various ways---through Black Consciousness politics and other attempts at refusing the ruinous articulation of biopolitics, sovereignty, and capital---submerged traditions of the Indian Ocean and the Black Atlantic offered them powerful resources. Of these, Chari reads Black documentary photography as particularly insightful audiovisual blues critique. At the tense interface of Marxism, feminism, and Black study, he offers a method and form of geography attentive to the spatial and embodied remains of history. Apartheid Remains looks out from South Durban to imaginations of abolition of all forms of racial capitalism and environmental suffering that define our planetary predicament.
Η βασική εκπαίδευση στην Ορμύλια Χαλκιδικής 1900-1950
Authors: Μπαντές Αθανάσιος
Published: April 2024

Η παρούσα μελέτη ερευνά τα εκπαιδευτικά δρώμενα στην Ορμύλια Χαλκιδικής κατά την περίοδο 1900-1950. Έχοντας ως επίκεντρο το δημοτικό σχολείο που λειτούργησε εκεί από το 1908 φιλοδοξεί να καταδείξει τον τρόπο της λειτουργίας του εντάσσοντάς τον όχι μόνο στο πλαίσιο της εκπαιδευτικής πραγματικότητας της εποχής αλλά και στο γενικότερο ιστορικοκοινωνικό γίγνεσθαι που το πλαισιώνει. Από αυτή την άποψη, όπως αρμόζει σε όλες τις μελέτες που αφορούν την ιστορία της εκπαίδευσης, στοχεύει να παρουσιάσει τη σχολική πραγματικότητα ως αναπόσπαστο τμήμα του κοινωνικού ιστού από τον οποίο διαμορφώνεται και ταυτόχρονα τον διαμορφώνει καταδεικνύοντας την αμφίδρομη σχέση της εκπαίδευσης με την κοινωνία. Η εργασία θα επικεντρωθεί στη μελέτη των σχολικών εγγράφων που έχουν διασωθεί με πληρότητα. Τα μαθητολόγια όλων των ετών (από το 1908 ως το 1950), οι γενικοί έλεγχοι, οι έλεγχοι διαγωγής, τα αποδεικτικά μεταγραφών και τα απολυτήρια αποτελούν τις κύριες πηγές της παρούσας έρευνας. Το Φιρμάνι του Αβδούλ Χαμίτ, η αρθρογραφία για την εποχή, οι προφορικές μαρτυρίες και οι αναφορές στην ευρύτερη εκπαιδευτική κατάσταση της Χαλκιδικής αποτελούν συμπληρωματικές πηγές που διαφωτίζουν πληρέστερα τη λειτουργία του σχολείου της Ορμύλιας όχι με τρόπο ξεκομμένο από το κλίμα της εποχής αλλά εντασσόμενο στο γενικότερο πλαίσιο της εκπαιδευτικής πραγματικότητας. Ως μέθοδος έρευνας υιοθετήθηκε η τεχνική της ανάλυσης περιεχομένου, που θεωρείται η προσφορότερη μέθοδος για τη μελέτη γραπτών τεκμηρίων και η οποία μπορεί να εφαρμοστεί σε επιλεγμένες πλευρές της ιστορικής έρευνας στην εκπαίδευση, όπως για παράδειγμα στην ανάλυση εκπαιδευτικών ντοκουμέντων. Η ιστορικο – συγκριτική μέθοδος συμπληρώνει την ανάλυση του περιεχομένου καθώς είναι σε θέση να αποσαφηνίζει την πορεία των εκπαιδευτικών τεκταινόμενων μέσα στις δεκαετίες. Τα συμπεράσματα που προκύπτουν από την έρευνα αυτή επιβεβαιώνουν την εκπαιδευτική ανισότητα που σχετίζεται πρωτίστως με την κοινωνική προέλευση και το φύλο. Τα κύρια θύματα της εκπαιδευτικής ανισότητας είναι τα παιδιά των αγροτών, των εργατών και οι γυναίκες. Βέβαια υπάρχει μια τάση εξισορρόπησης με το πέρασμα των χρόνων και την ένταξη του σχολείου στον κρατικό κορμό, αλλά σε καμία περίπτωση δεν μπορούμε να ισχυριστούμε την εξάλειψή τους. Οι φανερές αυτές εκπαιδευτικές ανισότητες θα ισχύσουν μέχρι το τέλος της υπό μελέτης περιόδου.
Morphology of gracilis muscle and the topographic anatomy of its neurovascular pedicles: A cross sectional study
Authors: Kumar Chettiar Ganesh , Vadgaonkar Rajanigandha , Prameela M.D. , Blossom Vandana , Murlimanju B.V. , Tonse Mamatha , Pai Mangala M.
Published: April 2024

Background The objective of this study was to perform morphometry of the gracilis muscle and understand the topographical basis of the entry of its pedicles. Methods We studied forty-four cadaveric lower extremities fixed in formalin. The length and width of the gracilis were measured at three locations: the origin, midpoint, and musculotendinous junction. The topographic location of the gracilis pedicles was also studied. Results The gracilis muscle’s length was 369.9±34.1 mm and 359.6±29.6 mm over the right and left sides. The width of right gracilis was 25±8.4 mm, 20.4±6.2 mm and 10.6±5.6 mm at the origin, midpoint and at the musculotendinous junction. The same over the left side were 26.7±8.6 mm, 20.6±9.1 mm and 10.4±6.4 mm respectively. The number of gracilis ranged from one to three. The location of first pedicle was 93.6±35.6 mm and 68.9±35.8 mm away from the pubic tubercle on the right and left sides, respectively. The second and third pedicles were entering at a distance of 153.1±38.8 mm and 101.3±20.8 mm, 214.6±86.8 mm and 145.3±124.4 mm over the right side and left side. The accessory head of the origin of the gracilis was observed in only one cadaver (2.3%), which originated from the adductor longus. Conclusions It is believed that the morphological data of the gracilis and its neurovascular pedicles will be enlightening to the operating surgeon. They will guide the procedures for reconstructive plastic surgery.
Pyuria in hospitalized general medical patients without urinary tract infection
Authors: Thyagaraju Praveenkumar , Mandal Jharna , Pari Thenmozhi Hariswar , Deepanjali Surendran
Published: April 2024

Urine microscopy for detecting pus cells is a common investigation ordered in hospitalized general medical patients as part of routine care. A few previous studies have shown that sterile pyuria is not uncommon in this population. We studied the prevalence of pyuria among patients hospitalized with non-urinary tract infection (UTI) diagnosis in the medical wards. We excluded patients with asymptomatic bacteriuria (ASB). Pyuria was quantified in uncentrifuged urine using the chamber counting method, and ≥ 10 pus cells per mm3 was considered significant. We also compared this method with the commonly used but less accurate method of counting pus cells/high power field using centrifuged urine (routine method). We studied 196 patients; 113 (57.7%) were males. Most (175[89.3%]) patients were hospitalized for an infection. We found that 18.4% of the study group had sterile pyuria, and it was strongly associated with the presence of concomitant microscopic hematuria (unadjusted odds ratio, 3.74 [1.65 to 8.50]; P=0.002). We found no association of pyuria with female gender, diabetes, acute kidney injury, or current antibiotic use. By routine method, 56 (28.6 %) patients had significant pyuria. In comparison to the chamber counting method, the routine method was 69.4(63—75.8) % sensitive and 80.6(75.1—86.2) % specific. The positive and negative predictive values were 44.6 (37.7— 51.6) % and 92.1 (88.4 — 95.9) %. We concluded that sterile pyuria and microscopic hematuria could be present in a proportion of hospitalized general medical patients without UTI or ASB. Clinical judgment is essential in interpreting the significance of abnormal urinalysis reports.