bluuebunny/crossref_metadata_2025 huggingface dataset:
Laser versus sham for genitourinary syndrome of menopause: A randomised controlled trial
Authors: Page Ann‐Sophie , Verbakel Jan Y. , Verhaeghe Johan , Latul Yani P. , Housmans Susanne , Deprest Jan
Published: November 2022

Objective

To assess whether CO2 laser treatment is more effective than sham application in relieving the most bothersome symptom (MBS) in women with genitourinary syndrome of menopause (GSM).

Design

Single‐centre, sham‐controlled, double‐blind, randomised trial.

Setting

A tertiary centre in Belgium.

Population

Sixty women with moderate to severe GSM symptoms.

Methods

All participants eventually received three consecutive laser and three consecutive sham applications, either first laser followed by sham, or conversely.

Main outcome measures

The primary outcome was the participant‐reported change in severity of the MBS at 12 weeks. Secondary outcomes included subjective (patient satisfaction, sexual function, urinary function) and objective (pH, Vaginal Health Index Score, in vivo microscopy) measurements assessing the short‐term effect and the longevity of treatment effects at 18 months after start of the therapy. Adverse events were reported at every visit.

Results

The MBS severity score decreased from 2.86 ± 0.35 to 2.17 ± 0.93 (−23.60%; 95% CI −36.10% to −11.10%) in women treated with laser compared with 2.90 ± 0.31 to 2.52 ± 0.78 (−13.20%; 95% CI −22.70% to −3.73%) in those receiving sham applications (p = 0.13). There were no serious adverse events reported up to 18 months.

Conclusions

In women with GSM, the treatment response 12 weeks after laser application was comparable to that of sham applications. There were no obvious differences for secondary outcomes and no serious adverse events were reported.
Evaluating the effectiveness of principles used for sharing resources of the Lower Ankobra Basin in the Western Region, Ghana
Authors: Mireku Dickson Okoree , Acheampong Peter Kwabena , Antwi Kwabena Barima , Hlovor Ishmael Kwabla
Published: November 2022

This paper evaluates the effectiveness of principles used for sharing resources of the Lower Ankobra River Basin found in the Western Region of Ghana. The purpose is to find out whether the institutions in charge of the management of the Lower Ankobra Basin are using principles prescribed by the United Nations Development Programme and the Sustainable Human Development (1997) for equitable sharing of the resources of the Lower Ankobra River Basin. The study adopted the descriptive research design. By means of in‐depth and semi‐structured interview guides, information was solicited from 268 respondents who played diverse roles in the conservation of the basin's resources. The paper found that management institutions fail to follow the right principles, such as equity, accountability, and efficiency, when distributing resources in the basin. The final results showed evidence of misallocation and uneven distribution of the basin's resources. It is recommended that the management institutions should periodically provide accurate, accessible, and comprehensible information on how resources have been utilized, by using community bulletin boards and social gatherings on behalf of users of the basin. In addition, to promote equity, the Government of Ghana must first compensate and reclaim all the lands in the basin from individuals whose activities impact negatively on its resources and hand them over to the Water Resources Commission for redistribution to more efficient areas of production based on the powers enshrined in Section 12 and 13 of the Water Management Act, Act 522, of Ghana.
Prognostic factors and genetic markers in thymic epithelial tumors: A narrative review
Authors: Agrafiotis Apostolos C. , Siozopoulou Vasiliki , Hendriks Jeroen M. H. , Pauwels Patrick , Koljenovic Senada , Van Schil Paul E.
Published: November 2022

Thymic epithelial tumors (TET) are a group of rare neoplasms of the anterior mediastinum comprising thymomas and thymic carcinomas. The carcinogenesis of TET is mostly unknown. Many studies, mostly retrospective case series, have tried to establish prognostic factors in TET. TET is a very heterogeneous group of tumors with many subtypes for which diagnosis and treatment remains a very challenging task. Despite the disparities among retrospective studies, there are some prognostic factors that are more pertinent such as the completeness of resection, TNM stage and the Masaoka‐Koga classification. On the other hand, the identification of different genetic pathways that result in the pathogenesis of TET represents a fascinating field of study that could possibly lead to the development of new targeted therapies. The aim of this review is to discuss the different prognostic factors and genetic markers of TET. The meticulous use of national and international databases could provide sufficient number of patients in order to draw more valid conclusions.
Chronic ethanol consumption exacerbates future stress‐enhanced fear learning, an effect mediated by dorsal hippocampal astrocytes
Authors: Barkell Gillian A. , Parekh Shveta V. , Paniccia Jacqueline E. , Martin Alia J. , Reissner Kathryn J. , Knapp Darin J. , Robinson Stacey L. , Thiele Todd E. , Lysle Donald T.
Published: November 2022

Background

Alcohol use disorder (AUD) and post‐traumatic stress disorder (PTSD) are highly comorbid, yet there is a lack of preclinical research investigating how prior ethanol (EtOH) dependence influences the development of a PTSD‐like phenotype. Furthermore, the neuroimmune system has been implicated in the development of both AUD and PTSD, but the extent of glial involvement in this context remains unclear. A rodent model was developed to address this gap in the literature.

Methods

We used a 15‐day exposure to the 5% w/v EtOH low‐fat Lieber‐DeCarli liquid diet in combination with the stress‐enhanced fear learning (SEFL) paradigm to investigate the effects of chronic EtOH consumption on the development of a PTSD‐like phenotype. Next, we used a reverse transcription quantitative real‐time polymerase chain reaction to quantify mRNA expression of glial cell markers GFAP (astrocytes) and CD68 (microglia) following severe footshock stress in EtOH‐withdrawn rats. Finally, we tested the functional contribution of dorsal hippocampal (DH) astrocytes in the development of SEFL in EtOH‐dependent rats using astrocyte‐specific Gi designer receptors exclusively activated by designer drugs (Gi‐DREADD).

Results

Results demonstrate that chronic EtOH consumption and withdrawal exacerbate future SEFL. Additionally, we found significantly increased GFAP mRNA expression in the dorsal and ventral hippocampus and amygdalar complex following the severe stressor in EtOH‐withdrawn animals. Finally, the stimulation of the astroglial Gi‐DREADD during EtOH withdrawal prevented the EtOH‐induced enhancement of SEFL.

Conclusions

Collectively, results indicate that prior EtOH dependence and withdrawal combined with a severe stressor potentiate future enhanced fear learning. Furthermore, DH astrocytes significantly contribute to this change in behavior. Overall, these studies provide insight into the comorbidity of AUD and PTSD and the potential neurobiological mechanisms behind increased susceptibility to a PTSD‐like phenotype in individuals with AUD.
Too transparent for signalling? A global analysis of bond issues by property companies
Authors: Berninger Marc , Bossong Paul , Schiereck Dirk , Steinhardt Marcel
Published: November 2022

Bond issues often result in negative revaluations of the market value of equity. These market reactions are usually explained by negative signals and asymmetric information about the use of the proceeds. In industries with rather transparent investment opportunities these arguments are not applicable and we expect to find no negative revaluations. Consequently, analysing the stock price reactions to 2299 bond issues by real estate companies between 1996 and 2019, we observe none to positive reactions on the announcement of an upcoming bond issue. The findings underpin the necessity for controlling of industry effects in empirical studies on capital structure decisions.
Role of lymphocyte immunization therapy (LIT) in repeated miscarriages – A review
Authors: Raut Mohan K. , Raut Mugdha M.
Published: November 2022

Recurrent Miscarriages are seen in 2%–5% of women and 50% of these are labelled as unexplained as no underlying cause is found in them. Various studies have explained possible alloimmune basis in these couples. Lymphocyte Immunization Therapy (LIT) was the earliest immunomodulatory method suggested in these cases. The efficacy of LIT was questioned by REMIS study in 1999 and subsequent Cochrane reviews. However, recent meta‐analyses have shown that LIT is not only effective in the treatment of repeated miscarriages but it is also safe. Review of the odds ratio for live birth of various meta‐analyses of studies in recurrent miscarriages has also shown that newer meta‐analyses have shown higher odds ratios. The purpose of this paper is to put forward the current perspective of LIT in reproductive failure and bring forth the recent evidence. In addition, we share our experience with the use of LIT in women with recurrent pregnancy losses. However, large multicentric RCTs are required to further prove efficacy of LIT.
Fossil Fuels and Fossil Kin: An Environmental Kin Study of Weaponised Fossil Kin and Alberta’sSo‐Called“Energy Resources Heritage”
Authors: Todd Zoe
Published: November 2022

Alberta produces 80% of the crude oil extracted in Canada. Canadian resource industry proponents and governments claim to be climate leaders, but Canada produces the highest per capita greenhouse gas emissions of all G20 countries, and is among the top ten carbon dioxide producers globally. Much of this pollution can be tied back to Alberta’s petro‐economy, an industry whose fossil wealth dates back millions of years to a time when flora and fauna were deposited in the lands and waters that Alberta now claims. Expanding on my earlier work on oil, gas, water, fish, and the Cree legal‐ethical principle of wahkohtowin in Alberta’s fossil‐scapes, this article examines what happens when the weaponised fossil kin of Alberta’s fossil and petro‐deposits are extracted and transformed into waste and pollution that disrupt reciprocal relationalities between human and nonhuman beings in Alberta’s watersheds, landscapes, atmospheres, and beyond.
Deep learning‐based diagnostic model for predicting complications after gastrectomy
Authors: Fukuyo Ryosuke , Tokunaga Masanori , Umebayashi Yuya , Saito Toshifumi , Okuno Keisuke , Sato Yuya , Saito Katsumasa , Fujiwara Naoto , Kinugasa Yusuke
Published: November 2022

Background

Gastric cancer is one of the leading causes of cancer deaths, and gastrectomy with lymph node dissection is the mainstay of treatment. Despite clinician efforts and advances in surgical methods, the incidence of complications after gastrectomy remains 10%–20% including fatalities. To the best of our knowledge, this is the first report on utilization of a deep learning method to build a new artificial intelligence model that could help surgeons diagnose these complications.

Methods

A neural network was constructed with a total of 4000 variables. Clinical, surgical, and pathological data of patients who underwent radical gastrectomy at our institute were collected to maintain a deep learning model. We optimized the parameters of the neural network to diagnose whether these patients would develop complications after gastrectomy or not.

Results

Seventy percent of the data was used to optimize the neural network parameters, and the rest was used to validate the model. A model that maximized the receiver operating characteristics (ROC) area under the curve (AUC) for validation of the data was extracted. The ROC‐AUC, sensitivity, and specificity of the model to diagnose all complications were 0.8 vs 0.7, 81% vs 50%, and 69% vs 75%, for the teaching and validation data, respectively.

Conclusions

A predictive model for postoperative complications after radical gastrectomy was successfully constructed using the deep learning method. This model can help surgeons accurately predict the incidence of complications on postoperative day 3.
Turning the lens in the study of precarity: On experimental social psychology's acquiescence to the settler‐colonial status quo in historic Palestine
Authors: Hakim Nader , Abi‐Ghannam Ghina , Saab Rim , Albzour Mai , Zebian Yara , Adams Glenn
Published: November 2022

This review examines the coloniality infused within the conduct and third reporting of experimental research in what is commonly referred to as the ‘Israeli‐Palestinian conflict’. Informed by a settler colonial framework and decolonial theory, our review measured the appearance of sociopolitical terms and critically analysed the reconciliation measures. We found that papers were three times more likely to describe the context through the framework of intractable conflict compared to occupation. Power asymmetry was often acknowledged and then flattened via, for instance, adjacent mentions of Israeli and Palestinian physical violence. Two‐thirds of the dependent variables were not related to material claims (e.g. land, settlements, or Palestinian refugees) but rather to the feelings and attitudes of Jewish Israelis and Palestinians. Of the dependent measures that did consider material issues, they nearly universally privileged conditions of the two‐state solution and compromises on refugees' right of return that would violate international law. The majority of the studies sampled Jewish–Israeli participants exclusively, and the majority of authors were affiliated with Israeli institutions. We argue that for social psychology to offer insights that coincide with the decolonization of historic Palestine, the discipline will have to begin by contextualizing its research within the material conditions and history that socially stratify the groups.
Anomalies in neurovascular coupling during early diabetes: A review
Authors: Fletcher Erica L. , Dixon Michael A. , Mills Samuel A. , Jobling Andrew I.
Published: November 2022

Diabetic retinopathy is the most feared complication for those with diabetes. Although visible vascular pathology traditionally defines the management of this condition, it is now recognised that a range of cellular changes occur in the retina from an early stage of diabetes. One of the most significant functional changes that occurs in those with diabetes is a loss of vasoregulation in response to changes in neural activity. There are several retinal cell types that are critical for mediating so‐called neurovascular coupling, including Müller cells, microglia and pericytes. Although there is a great deal of evidence that suggests that Müller cells are integral to regulating the vasculature, they only modulate part of the vascular tree, highlighting the complexity of vasoregulation within the retina. Recent studies suggest that retinal immune cells, microglia, play an important role in mediating vasoconstriction. Importantly, retinal microglia contact both the vasculature and neural synapses and induce vasoconstriction in response to neurally expressed chemokines such as fractalkine. This microglial‐dependent regulation occurs via the vasomediator angiotensinogen. Diabetes alters the way microglia regulate the retinal vasculature, by increasing angiotensinogen expression, causing capillary vasoconstriction and contributing to a loss of vascular reactivity to physiological signals. This article summarises recent studies showing changes in vascular regulation during diabetes, the potential mechanisms by which this occurs and the significance of these early changes to the progression of diabetic retinopathy.
Effects of different management strategies on long‐term trends of Australian threatened and near‐threatened mammals
Authors: Tulloch Ayesha I. T. , Jackson Micha V. , Bayraktarov Elisa , Carey Alexander R. , Correa‐Gomez Diego F. , Driessen Michael , Gynther Ian C. , Hardie Mel , Moseby Katherine , Joseph Liana , Preece Harriet , Suarez‐Castro Andrés Felipe , Stuart Stephanie , Woinarski John C. Z. , Possingham Hugh P.
Published: November 2022

Monitoring is critical to assess management effectiveness, but broadscale systematic assessments of monitoring to evaluate and improve recovery efforts are lacking. We compiled 1808 time series from 71 threatened and near‐threatened terrestrial and volant mammal species and subspecies in Australia (48% of all threatened mammal taxa) to compare relative trends of populations subject to different management strategies. We adapted the Living Planet Index to develop the Threatened Species Index for Australian Mammals and track aggregate trends for all sampled threatened mammal populations and for small (<35 g), medium (35–5500 g), and large mammals (>5500 g) from 2000 to 2017. Unmanaged populations (42 taxa) declined by 63% on average; unmanaged small mammals exhibited the greatest declines (96%). Populations of 17 taxa in havens (islands and fenced areas that excluded or eliminated introduced red foxes [Vulpes vulpes] and domestic cats [Felis catus]) increased by 680%. Outside havens, populations undergoing sustained predator baiting initially declined by 75% but subsequently increased to 47% of their abundance in 2000. At sites where predators were not excluded or baited but other actions (e.g., fire management, introduced herbivore control) occurred, populations of small and medium mammals declined faster, but large mammals declined more slowly, than unmanaged populations. Only 13% of taxa had data for both unmanaged and managed populations; index comparisons for this subset showed that taxa with populations increasing inside havens declined outside havens but taxa with populations subject to predator baiting outside havens declined more slowly than populations with no management and then increased, whereas unmanaged populations continued to decline. More comprehensive and improved monitoring (particularly encompassing poorly represented management actions and taxonomic groups like bats and small mammals) is required to understand whether and where management has worked. Improved implementation of management for threats other than predation is critical to recover Australia's threatened mammals.
Antecedents of top management team and board gender diversity: A review and an agenda for research
Authors: Yao Ting
Published: November 2022

Research Question/Issue

The paper aims to understand the factors hindering and facilitating women's access to top management teams (TMTs) and boards of directors. It provides a systematic review of extant scholarly work on the antecedents of TMT and board gender diversity.

Research Findings/Insights

Reviewing and integrating research from over 200 journal publications, I develop an integrative review of the antecedents of gender diversity for two types of research contexts—TMT and board—at three levels: person centered, situation centered, and social‐system centered. I also identify knowledge gaps and suggest areas for future research.

Theoretical/Academic Implications

This comprehensive review of extant research simultaneously considers antecedents of TMT gender diversity and board gender diversity, providing insights into divergent trends of TMT and board gender diversity while highlighting understudied areas. Hopefully, the review will inspire more research to advance knowledge of the antecedents of TMT and board gender diversity, areas that have received relatively little attention compared with extensive research on the consequences of gender diversity.

Practitioner/Policy Implications

Gender diversity in corporate leadership is a topic of great interest. The growth in board gender diversity is unprecedented, but growth in TMT gender diversity has been stagnant. I offer a synthesis of extant literature to understand the social, situational, and individual drivers of TMT and board gender diversity, providing valuable insights for policymakers, investors, executives, and directors who seek to improve corporate leadership gender diversity.
Pediatric CYP2D6 metabolizer status and post‐tonsillectomy nausea and vomiting after ondansetron
Authors: Black Katherine , Brenn B. Randall , Gaedigk Andrea , Wanderer Jonathan P. , Van Driest Sara L.
Published: November 2022

The goal of this study was to determine whether CYP2D6 metabolizer status within the ondansetron‐treated pediatric tonsillectomy population is associated with risk of postoperative nausea and vomiting (PONV) in the post‐anesthesia care unit. We conducted a retrospective cohort study of pediatric patients (<18 years) who underwent tonsillectomy and received ondansetron on the day of the procedure. Data were obtained from BioVU, an institutional biobank that links DNA to de‐identified electronic health record data. Subjects were tested for 10 CYP2D6 allelic variants and copy number variation, and genotype data translated into CYP2D6 metabolizer status. The cohort included 652 individuals, 105 (16.1%) of whom had PONV. Rates of PONV were similar across groups: ultrarapid metabolizers (UMs), 1 of 9 (11.1%); normal metabolizers (NMs), 64 of 354 (18.1%); intermediate metabolizers (IMs), 33 of 234 (14.1%); poor metabolizers (PMs), 6 of 39 (15.4%); and ambiguous phenotypes, 1 of 16 (6.3%). In multivariable analysis adjusted for age, sex, and time under anesthesia, CYP2D6 metabolizer status was not associated with PONV, with an odds ratio of 1.37 (95% confidence interval 0.9, 2.1) when comparing PM/IM versus NM/UM. In this large pediatric population, no significant differences were detected for PONV based on CYP2D6 metabolizer status. Further investigation is needed to determine mechanisms for ondansetron inefficacy in children.
Chordoma metastatic to skin: A report of two cases and a brief review of the literature
Authors: Dimopoulos Yiannis P. , Ivan Doina , Prieto Victor G. , Aung Phyu P.
Published: November 2022

Chordomas are rare, locally aggressive tumors of notochordal origin usually arising in the spine or base of the skull. Skin involvement is rare and typically occurs via direct extension of the primary tumor to the skin. Although there are increasing reports of the skin being involved as a distant metastatic site in patients with chordoma, this remains an exceedingly rare occurrence. We present two cases of patients diagnosed with metastasis of chordoma to the skin that represented distant metastasis. In the first case, a patient with a primary thoracic/lumbar chordoma presented with isolated metastasis to the skin of the left lower jaw 9 years after initial diagnosis of the chordoma. To our knowledge, this is the first reported case of a chordoma of this site to develop distant skin metastasis. In the second case, a patient with a primary sacral chordoma presented with metastasis to the skin of the right side of his chin 6 years after initial diagnosis of the chordoma, following previous metastatic spread to the liver and lung. Finally, we briefly review the literature on chordoma metastasis to the skin and highlight salient features to raise awareness of this uncommon occurrence.
Serial pancreatic juice aspiration cytologic examination with balloon‐assisted enteroscopy in surgically altered anatomy
Authors: Mie Takafumi , Sasaki Takashi , Sasahira Naoki
Published: November 2022

Watch a video of this article.
The relationship between pesi score and pulmonary venous flow parameters in patients with acute pulmonary embolism
Authors: Aydınyılmaz Faruk , Özbeyaz Nail Burak , Algül Engin , Aksakal Alperen , Guliyev İlkin , Şahan Haluk Furkan , Aksakal Emrah , Saraç İbrahim , Kalkan Kamuran
Published: November 2022

Background

Acute pulmonary embolism (APE) is an important cause of cardiovascular morbidity and mortality. PESI scoring is used in risk classification. This study was designed to determine the relationship between echocardiographic pulmonary vein measurements and PESI score, which is an important tool in diagnosis and treatment.

Methods

A total of 210 patients were evaluated. Pulmonary vein measurements and PESI scores of the patients at the time of diagnosis were calculated. Correlation analysis was performed to determine the relationship between the two parameters.

Results

Total PESI scores were 112.9 ± 33.9. The pulmonary vein S wave .39 ± .14, the D wave .48 ± .18, and the S/D ratio was found to be .86 ± .35. It was determined that there was a significant correlation between pulmonary S/D ratio and PESI score. (Pearson correlation coefficient = −.693, R2 Linear:.484; p < .001) The AUC of S/D for mortality prediction was .729 (95% CI = .653–.804; p < .001), the cutoff value was .63, the sensitivity and specificity were 55.6% and 55.7%, respectively.

Conclusion

Pulmonary vein measurements were found to be correlated with the PESI score and were found to be a parameter that could predict mortality.
Mortality and basal area growth following precommercial thinning in stands affected by Armillaria, Laminated and Tomentosus root diseases in southern British Columbia
Authors: Morrison Duncan J. , Rönnberg Jonas , Pellow Kevin , Cleary Michelle
Published: November 2022

Precommercial thinning aims to reduce the density of immature stands to stimulate growth of well‐spaced crop trees of preferred species and free from defects and disease. The chronic persistence of Armillaria, Laminated and Tomentosus root diseases in coniferous forests of British Columbia, Canada may offset potential gains in timber yield of commercially important tree species by creating stumps that the fungi utilize as an energy source to infect neighbouring trees. In juvenile plantations and naturally regenerated stands in six biogeoclimatic (BEC) zones with evidence of root disease caused by Armillaria ostoyae (8 sites), Coniferiporia sulphurascens (2 sites) or Onnia tomentosa (1 site), five of ten 20 m square plots per site were randomly selected for thinning to British Columbia Ministry of Forests specifications. Crop tree diameter at breast height and mortality from all causes were recorded at establishment and periodically thereafter up to 19 years post‐thinning. Logistic regression analysis of mortality rates showed significant differences among root disease pathogens, between planted and natural stands, and among ecological zones. Yet over all sites, differences between thinned and control plots were not significant. At the final assessment, crop tree basal area was higher in thinned than in control plots at 10 of 11 sites. Root disease, including infected and dead trees and other lethal biotic and abiotic agents, reduced potential yield in both treatments (thinned and control). At several Armillaria sites, mortality was slightly to substantially higher in thinned than in control plots, suggesting that thinning can increase the amount and potential of inoculum which may continue to adversely impact productivity of those stands. Recommendations for silvicultural management of the three root diseases are discussed.
Successful removal of a functional parathyroid adenoma using a radio‐guided parathyroidectomy technique with a hand‐held gamma detector and technetium Tc 99m sestamibi scintigraphy in a horse
Authors: Connard Shannon S. , Hodge Elizabeth A. , Demchur Jolie A. , Wulster Kathryn B. , Johnson Amy L. , Ross Michael W. , Levine David G.
Published: November 2022

This clinical case report details the use of a radio‐guided parathyroidectomy technique using a hand‐held gamma detector and technetium Tc 99m sestamibi scintigraphy for detection and removal of a functional parathyroid adenoma in a horse. An 18‐year‐old Arabian gelding was diagnosed with primary hyperparathyroidism based on persistent hypercalcaemia and increased parathyroid hormone concentration. Single gland disease was suspected after technetium Tc 99m sestamibi scintigraphy showed focal increased radiopharmaceutical uptake (IRU) at the thoracic inlet. Ultrasonography failed to identify a discrete mass in the region of IRU. Surgical excision was recommended; however, due to unreliable preoperative localisation, a radio‐guided parathyroidectomy technique was elected. A radio‐guided parathyroidectomy technique was performed under general anaesthesia using a hand‐held gamma detector and technetium Tc 99m sestamibi scintigraphy to identify the parathyroid adenoma, which was subsequently excised. The horse recovered from the procedure without complication. Successful removal of the parathyroid adenoma was confirmed based on histopathological and serum bioch findings. Following the procedure, the horse showed no evidence of hyperparathyroidism and returned to light pleasure riding. Three years postoperatively, the gelding died of unrelated natural causes; a post‐mortem examination was not performed. This radio‐guided parathyroidectomy technique was effective in facilitating the removal of a parathyroid adenoma in this gelding and might be useful in other equids that have primary hyperparathyroidism IRU on technetium Tc 99m sestamibi scintigraphy, particularly if a discrete mass cannot be identified ultrasonographically.
Ginsenoside compound K suppresses tumour growth in the 22Rv1 xenograft model and inhibits androgenic responses via the transcriptional mechanism in human prostate cancer cells
Authors: Jiang Mingyue , Sun You , Song Kyung
Published: November 2022

Androgen receptor (AR) signalling is known to be dispensable for the biology of castration‐resistant prostate cancer (CRPC), whereas the AR itself and the residual androgens after castration are crucial for the growth and progression of CRPC. Therefore, there is high demand for novel therapeutic candidates targeting AR itself or aberrant AR signalling to suppress the progression to or the growth of CPRC. Here, we report that ginsenoside compound K (GCK), the primary bioactive metabolite biotransformed from protopanaxadiol (PPD) ginsenoside, acts as a novel AR signalling inhibitor by transcriptionally suppressing AR expression and tumour growth in athymic nude mice. GCK inhibited cell growth in LNCaP, PC‐3 and 22Rv1 prostate cancer cell lines and suppressed the expression levels of cell cycle regulators. GCK down‐regulated epithelial–mesenchymal transition markers such as vimentin and matrix metalloproteinase 9 (MMP9), whereas E‐cadherin was significantly increased in GCK‐stimulated LNCaP and 22Rv1 cells. Moreover, GCK treatment markedly decreased both AR and AR‐V7 protein levels in LNCaP and 22Rv1 cells, possibly by decreasing AR promoter activity. Experiments with AR promoter‐deleted constructs revealed that the region between −412 and −227 is critical for GCK regulation. GCK treatment in athymic nude mice implanted with 22Rv1 CRPC cell lines significantly suppressed tumour growth and AR expression levels in tumour tissues. Collectively, our results suggest that GCK, as a novel AR inhibitor, could be a potential therapeutic agent against prostate cancer and an effective chemopreventive agent to delay the progression to CRPC.
Clinicopathological features of rhabdomyosarcoma with novel FET::TFCP2 and TIMP3::ALK fusion: report of two cases and literature review
Authors: Duan Fang‐Lei , Yang Hong , Gong Xiaojin , Zuo Zuo , Qin Sheng , Ji Juan , Zhou Chengmin , Dai Jie , Guo Peng , Liu Yang
Published: November 2022

Aims

The aim of this study was to evaluate the clinicopathological features, immunophenotype, differential diagnosis, molecular genetic features and prognosis of spindle cell rhabdomyosarcoma with TFCP2 rearrangement.

Methods

Two cases of spindle cell rhabdomyosarcoma with FET::TFCP2 gene fusion were included in this study. Samples were collected and evaluated through histological observation, immunohistochemistry, fluorescence in‐situ hybridisation and high‐throughput gene sequencing and previous findings.

Results

The tumour tissues mainly comprised spindle cells and epithelioid cells, which expressed striated muscle markers, and exhibited high expression levels of CK and ALK protein markers. Molecular detection showed that the FET::TFCP2 gene was fused. A rare case with TIMP3::ALK and FUS::TFCP2 double‐fusion was observed in this study.

Conclusions

A case with double fusion of ALK and TFCP2 was reported in rhabdomyosarcoma for the first time in this study, which provides information on the molecular characteristic of the tumour. Spindle cell rhabdomyosarcoma with FET::TFCP2 fusion is characterised by histological, immunohistochemical and genetic changes. The tumour is aggressive, with poor prognosis and poor response to radiotherapy and chemotherapy. The efficacy of targeted therapy for ALK should be explored through more clinical studies.
Improving mitotic cell counting accuracy and efficiency using phosphohistone‐H3 (PHH3) antibody counterstained with haematoxylin and eosin as part of breast cancer grading
Authors: Ibrahim Asmaa , Toss Michael S. , Makhlouf Shorouk , Miligy Islam M. , Minhas Fayyaz , Rakha Emad A.
Published: November 2022

Background

Mitotic count in breast cancer is an important prognostic marker. Unfortunately, substantial inter‐ and intraobserver variation exists when pathologists manually count mitotic figures. To alleviate this problem, we developed a new technique incorporating both haematoxylin and eosin (H&E) and phosphorylated histone H3 (PHH3), a marker highly specific to mitotic figures, and compared it to visual scoring of mitotic figures using H&E only.

Methods

Two full‐face sections from 97 cases were cut, one stained with H&E only, and the other was stained with PHH3 and counterstained with H&E (PHH3–H&E). Counting mitoses using PHH3–H&E was compared to traditional mitoses scoring using H&E in terms of reproducibility, scoring time, and the ability to detect mitosis hotspots. We assessed the agreement between manual and image analysis‐assisted scoring of mitotic figures using H&E and PHH3–H&E‐stained cells. The diagnostic performance of PHH3 in detecting mitotic figures in terms of sensitivity and specificity was measured. Finally, PHH3 replaced the mitosis score in a multivariate analysis to assess its significance.

Results

Pathologists detected significantly higher mitotic figures using the PHH3–H&E (median ± SD, 20 ± 33) compared with H&E alone (median ± SD, 16 ± 25), P < 0.001. The concordance between pathologists in identifying mitotic figures was highest when using the dual PHH3–H&E technique; in addition, it highlighted mitotic figures at low power, allowing better agreement on choosing the hotspot area (k = 0.842) in comparison with standard H&E (k = 0.625). A better agreement between image analysis‐assisted software and the human eye was observed for PHH3‐stained mitotic figures. When the mitosis score was replaced with PHH3 in a Cox regression model with other grade components, PHH3 was an independent predictor of survival (hazard ratio [HR] 5.66, 95% confidence interval [CI] 1.92–16.69; P = 0.002), and even showed a more significant association with breast cancer‐specific survival (BCSS) than mitosis (HR 3.63, 95% CI 1.49–8.86; P = 0.005) and Ki67 (P = 0.27).

Conclusion

Using PHH3–H&E‐stained slides can reliably be used in routine scoring of mitotic figures and integrating both techniques will compensate for each other's limitations and improve diagnostic accuracy, quality, and precision.
Gender differences in suicidal ideation, suicide attempts, and suicide death among people living with HIV: A systematic review and meta‐analysis
Authors: Hu Fei‐Hong , Zhao Dan‐Yan , Fu Xue‐Lei , Zhang Wan‐Qing , Tang Wen , Hu Shi‐Qi , Shen Wang‐Qin , Chen Hong‐Lin
Published: November 2022

Objective

Although excess mortality, especially suicide, is a critical trait in people living with HIV, consensus about gender differences in these areas is lacking. We conducted meta‐analyses to examine gender differences in suicidal ideation, suicide attempts, and suicide death among people living with HIV.

Methods

We systematically searched PubMed and Web of Science for studies written in English. In this review, suicide among people living with HIV includes suicide death, suicidal ideation, and suicide attempts. Studies reporting the suicide prevalence among males and females living with HIV were eligible for inclusion in our review. Odds ratios (ORs) and 95% confidence intervals (CIs) served as the effect size index. Fixed‐effects or random‐effects meta‐analyses were chosen based on the size of the heterogeneity.

Results

A total of 27 studies comprising 801 017 participants from 11 countries were included in the meta‐analysis. The overall prevalence of suicidal ideation was 18.0% (95% CI 13.3%–22.8%) in males and 20.8% (95% CI 16.4%–25.1%) in females, and there was a statistically significant higher risk of suicidal ideation in females living with HIV (OR 1.30; 95% CI 1.09–1.56; p < 0.05). The overall prevalence of suicide attempts was 16.8% (95% CI 9.0%–24.5%) in males and 24.7% (95% CI 12.4%–37.1%) in females, and there was a statistically significant higher risk of suicide attempts in females living with HIV (OR 1.34; 95% CI 1.02–1.75; p < 0.05). The pooled prevalence of suicide death was 1.2% (95% CI 0.5%–1.9%) among males and 0.2% (95% CI 0.1%–0.3%) among females, and the risk of suicide death between genders was not statistically significant (OR 0.78; 95% CI 0.50–1.24; p = 0.298).

Conclusions

There were gender differences in suicidal ideation and suicide attempts among people living with HIV. Females living with HIV were more likely to experience suicidal ideation and make suicide attempts, but there were no statistically significant gender differences in suicide death. Appropriate initiatives to optimize the recognition, treatment, and management suicide behaviours of males and females living with HIV may narrow this gender gap.
The impact of loneliness on compliance with COVID‐19 prevention guidelines
Authors: Schultz Ainslie E. , Newman Kevin P.
Published: November 2022

Many individuals have been reluctant to follow the COVID‐19 prevention guidelines (e.g., wearing a mask, physical distancing, and vigilant handwashing) set forth by the U.S. Center for Disease Control to reduce the spread of COVID‐19. In this research, we use reciprocal altruism theory to investigate the role of loneliness and its impact on compliance with these guidelines. Our findings indicate that lonely individuals are less willing to comply with COVID‐19 prevention guidelines than non‐lonely individuals. Process evidence suggests that this occurs as loneliness can inhibit an individual's sense of obligation to reciprocate to others. However, we demonstrate that framing information about COVID‐19 through agentic (vs. communal) advertising messaging strategies can offset the negative impact of loneliness on compliance with COVID‐19 prevention guidelines. Thus, marketers and policymakers may want to consider the important role of loneliness when tailoring messaging appeals that encourage compliance with COVID‐19 prevention guidelines.
Biological and prognostic implications of biopsy upgrading for high‐grade upper tract urothelial carcinoma at nephroureterectomy
Authors: Katayama Satoshi , Pradere Benjamin , Grossman Nico C. , Potretzke Aaron M. , Boorjian Stephen A. , Ghoreifi Alireza , Daneshmand Sia , Djaladat Hooman , Sfakianos John P. , Mari Andrea , Khene Zine‐Eddine , D'Andrea David , Hayakawa Nozomi , Breda Alberto , Fontana Matteo , Fujita Kazutoshi , Antonelli Alessandro , van Doeveren Thomas , Steinbach Christina , Mori Keiichiro , Laukhtina Ekaterina , Rouprêt Morgan , Margulis Vitaly , Karakiewicz Pierre I. , Araki Motoo , Compérat Eva , Nasu Yasutomo , Shariat Shahrokh F.
Published: November 2022

Objectives

Technical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated.

Methods

Patients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low‐grade on URS biopsy) versus same grade (high‐grade on URS biopsy) for high‐grade UTUC tumors on radical nephroureterectomy (RNU) specimens.

Results

This study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy‐based low‐ and high‐grade tumors, respectively. Median follow‐up was 27.3 months. Patients with high‐grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p < 0.001) and positive lymph nodes (LNs; p < 0.001). On multivariable analyses adjusting for the established risk factors, high‐grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10–2.75; p = 0.018), cancer‐specific (HR 1.94; 95% CI, 1.07–3.52; p = 0.03), and recurrence‐free survival (HR 1.80; 95% CI, 1.13–2.87; p = 0.013). In subgroup analyses of patients with pT2‐T4 and/or positive LN, its significant association retained. Furthermore, high‐grade biopsy in clinically non‐muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (≥pT2) compared to low‐grade biopsy.

Conclusions

High tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low‐grade UTUC that becomes upgraded to high‐grade might carry a better prognosis than high‐grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high‐grade on RNU.
Dysfunctional phenotype of systemic and pulmonary regulatory T cells associate with lethal COVID‐19 cases
Authors: Gonçalves‐Pereira Marcela Helena , Santiago Luciana , Ravetti Cecilia Gómez , Vassallo Paula Frizera , de Andrade Marcus Vinicius Melo , Vieira Mariana Sousa , de Fátima Souza de Oliveira Fernanda , Carobin Natália Virtude , Li Guangzhao , de Paula Sabino Adriano , Nobre Vandack , da Costa Santiago Helton
Published: November 2022

Severe cases of COVID‐19 present hyperinflammatory condition that can be fatal. Little is known about the role of regulatory responses in SARS‐CoV‐2 infection. In this study, we evaluated the phenotype of regulatory T cells in the blood (peripheral blood mononuclear cell) and the lungs (broncho‐alveolar) of adult patients with severe COVID‐19 under invasive mechanical ventilation. Our results show important dynamic variation on Treg cells phenotype during COVID‐19 with changes in number and functional parameters from the day of intubation (Day 1 of intensive care unit admission) to Day 7. We observed that compared with surviving patients, non‐survivors presented lower numbers of Treg cells in the blood. In addition, lung Tregs of non‐survivors also displayed higher PD1 and lower FOXP3 expressions suggesting dysfunctional phenotype. Further signs of Treg dysregulation were observed in non‐survivors such as limited production of IL‐10 in the lungs and higher production of IL‐17A in the blood and in the lungs, which were associated with increased PD1 expression. These findings were also associated with lower pulmonary levels of Treg‐stimulating factors like TNF and IL‐2. Tregs in the blood and lungs are profoundly dysfunctional in non‐surviving COVID‐19 patients.
A joint normal‐binary (probit) model
Authors: Delporte Margaux , Fieuws Steffen , Molenberghs Geert , Verbeke Geert , Situma Wanyama Simeon , Hatziagorou Elpis , De Boeck Christiane
Published: November 2022

In biomedical research, often hierarchical binary and continuous responses need to be jointly modelled. In joint generalised linear mixed models, this can be done with correlated random effects, which allows examining the association structure between the various responses and the evolution of this association over time. In addition, the effect of covariates on all outcomes can be assessed simultaneously. Still, investigating this association is often limited to examining the correlations between the responses on an underlying scale. In addition, the interpretation of this hierarchical model is conditional on the subject‐specific random effects. This paper extends this approach and shows how manifest correlations can be computed, that is, the associations between the observed responses. Further, a marginal model is formulated, in which the interpretation is no longer conditional on the random effects. In addition, prediction intervals are derived of one subvector of responses conditional on the other. These methods are applied in a case study of the lung function and allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.
CXC‐ receptor 2 promotes extracellular matrix production and attenuates migration in peripapillary human scleral fibroblasts under mechanical strain
Authors: Qiu Chen , Wang Chuandong , Sun Xinghuai , Xu Jianjiang , Wu Jihong , Zhang Rong , Li Gang , Xue Kang , Zhang Xiaoling , Qian Shaohong
Published: November 2022

As the main loading‐bearing tissue of eye, sclera exerts an important role in the pathophysiology of glaucoma. Intraocular pressure (IOP) generates mechanical strain on sclera. Recent studies have demonstrated that sclera, especially the peripapillary sclera, undergoes complicated remodelling under the mechanical strain. However, the mechanisms of the hypertensive scleral remodelling in human eyes remained uncertain. In this study, peripapillary human scleral fibroblasts (ppHSFs) were applied cyclic mechanical strain by Flexcell‐5000™ tension system. We found that CXC‐ ligands and CXCR2 were differentially expressed after strain. Increased cell proliferation and inhibited cell motility were observed when CXCR2 was upregulated under the strain, whereas cell proliferation and motility did not have a significant change when CXCR2 was knocked down. CXCR2 could facilitate cell proliferation ability, modulate the mRNA and protein expressions of type I collagen and matrix metalloproteinase 2 via JAK1/2‐STAT3 signalling pathway. In addition, CXCR2 might inhibit cell migration via FAK/MLC2 pathway. Taken together, CXCR2 regulated protein production and affected cell behaviours of ppHSFs. It might be a potential therapeutic target for the hypertensive scleral remodelling.
A novel composite colorimetric sensor array for quality characterization of shrimp paste based on indicator displacement assay and etching of silver nanoprisms
Authors: Jiao Xueya , Huang Xingyi , Yu Shanshan , Wang Li , Wang Yu , Zhang Xiaorui , Ren Yi
Published: November 2022

In this study, a novel amino acids and salts‐sensitive colorimetric sensor array (CSA) was constructed to evaluate shrimp paste quality based on mechanisms of indicator displacement assay (IDA) and silver nanoprisms (AgNPRs) etching. Three supervised learning methods including linear discriminant analysis (LDA), K‐nearest neighbor (KNN), and Support Vector Machine (SVM) were applied to qualitatively distinguish shrimp paste from different geographical origins with the discriminant accuracy for prediction set of 94.44%, 97.22%, and 100%, respectively. Partial least squares (PLS) and SVM were further used to quantitatively predict the crucial compounds in shrimp paste. The correlation coefficients for prediction set (Rp) of amino acid nitrogen and salt using PLS model were 0.8875 and 0.9478, respectively. And the prediction performance was significantly improved by using SVM analysis with Rp of 0.9312 and 0.9500, respectively. The results indicated that the CSA can be an effective tool in the quality characterization of shrimp paste.

Practical applications

A novel amino acids and salts‐sensitive colorimetric sensor array (CSA) was constructed to evaluate shrimp paste quality based on mechanisms of indicator displacement assay (IDA) and silver nanoprisms (AgNPRs) etching.

This study combined CSA with pattern recognition methods including LDA, KNN, and SVM modeling methods to effectively identify six different shrimp pastes with the highest recognition rate of the SVM model (100% for both training set and prediction set).

Partial least squares (PLS) and SVM modeling methods were further applied to quantitatively predict the amino acid nitrogen and salt content of six different types of shrimp pastes with an excellent prediction performance.