bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case of immune-complex mediated glomerulonephritis associated with pembrolizumab
Authors: Bonilla Marco , Bijol Vanesa , Corona Antonio Gabriel De Leon , Sullivan Kevin M. , Jhaveri Kenar D. 
Published: December 2021

Introduction: Immune checkpoint inhibitors (ICI) are changing the way we treat cancer. However, these novel agents have various systemic adverse events that may preclude its use and cause poor patient outcomes. ICI-associated acute kidney injury is an emerging complication of this treatment. While tubulointerstitial disease is the most common pathologic finding of patients with ICI-associated AKI, there is sparse data in medical literature describing its association with glomerular disease. Case report: Here, we present a patient with metastatic lung adenocarcinoma who developed acute kidney injury and significant proteinuria after receiving pembrolizumab. The kidney biopsy revealed a membranoproliferative and diffuse segmental endocapillary proliferative pattern of glomerular injury. Management and outcome: Pembrolizumab was then held and high-dose prednisone was initiated, resulting in a rapid and dramatic improvement in kidney function and proteinuria. Discussion: We highlight a report of a patient diagnosed with immune-complex mediated glomerulonephritis associated with the use of pembrolizumab, who was successfully treated with drug withdrawal and corticosteroids.
Brolucizumab for persistent macular fluid in neovascular age-related macular degeneration after prior anti-VEGF treatments
Authors: Hussain Rehan M. , Neal Andrea , Yannuzzi Nicolas A. , Patel Kevin H. , Huo Siya , Hariprasad Seenu M. , Bhatia Sumit P. 
Published: December 2021

Background: Some patients with neovascular age-related macular degeneration (nAMD) have persistent intraretinal/subretinal fluid (IRF/SRF) despite being treated with anti-VEGF agents. There is limited data on efficacy of switching to intravitreal brolucizumab (IVBr) in these patients. Purpose: To determine anatomic and visual outcomes of eyes with nAMD treated with for persistent IRF/SRF. Methods: Retrospective series of eyes with nAMD treated initially with aflibercept (IVA, n = 48) and bevacizumab (IVBe, n = 10), then switched to IVBr for persistent IRF/SRF. Results: In the IVA-IVBr group, a mean of 42 days after one IVBr, mean logMAR changed from 0.50 to 0.49 ( p = 0.73) and mean CSFT changed from 340 to 305 µm ( p < 0.001); 31% of eyes had no fluid, 42% had persistent but reduced fluid, 25% had stable fluid, and 2% had increased fluid. For a subgroup of 25 eyes that completed a series of 3 IVBr, mean logMAR changed from 0.44 to 0.40 ( p = 0.35) and mean CSFT changed from 325 to 277 µm ( p = 0.001); 24% of eyes had no fluid at last follow-up, a mean of 54 days after last IVBr. In the IVBe-IVBr group, a mean of 44 days after one IVBr, mean logMAR changed from 0.46 to 0.40 ( p = 0.114) and mean CSFT from 401 to 325 µm ( p = 0.009); 30% of eyes had no fluid and 70% had persistent but reduced fluid. For a subgroup of four eyes that completed a series of three IVBr, mean logMAR changed from 0.33 to 0.35 ( p = 0.391) and mean CSFT improved from 375 to 275 µm ( p = 0.001); 50% of eyes had no fluid at last follow-up, a mean of 65 days after last IVBr. Conclusion: In nAMD eyes previously treated with IVA and IVBe, switching to IVBr significantly reduced persistent IRF/SRF but did not significantly affect visual outcomes.
A Comparison of Different Thyroid Imaging Reporting and Data Systems to Reduce Unnecessary FNAs and Missed Malignancies
Authors: Seif Ehsan , Qorbani Mostafa , Mousavi Shaghayegh , Salahshoor Ali 
Published: December 2021

Objective: The Thyroid Imaging Reporting and Data System (TIRADS) has been proposed to reduce the number of unnecessary fine needle aspirations (FNA) from thyroid nodules. Materials and Methods: An individual radiologist provided sonographic examinations and FNA on a collection of 188 thyroid nodules. The recommendations based on the TIRADS system, for each nodule, was determined and evaluated against the cytology results. Results: The American College of Radiology (ACR), artificial intelligence (AI), European (EU), and Korean (K) scoring systems reduced FNAs by 53%, 56%, 48%, and 28%, respectively. Among those lesions without a recommendation for immediate FNA, The ACR would have missed four malignant nodules, the AI would have missed four malignant nodules, and K TIRADS would have missed three malignant nodules but with a recommended follow-up imaging. The ACR would have missed three malignant nodules, the AI would have missed four malignant nodules, and EU TIRADS would have missed four malignant nodules, without a recommended follow-up examination. The highest and lowest kappa interrelated agreements were between ACR and AI (0.902) and AI and K (0.448). Conclusion: The ACR and AI TIRADS could substantially decrease the number of FNAs but rely on follow-up imaging. The EU TIRADS reduced the number of FNAs, the least however this system had less dependence on follow-up imaging. The K TIRADS was the most conservative method and the least dependent on follow-up diagnostics.
Rab31-dependent regulation of transforming growth factor ß expression in breast cancer cells
Authors: Soelch Susanne , Beaufort Nathalie , Loessner Daniela , Kotzsch Matthias , Reuning Ute , Luther Thomas , Kirchner Thomas , Magdolen Viktor 
Published: December 2021

Abstract
Background
The small GTP-binding protein Rab31 plays an important role in the modulation of tumor biological-relevant processes, including cell proliferation, adhesion, and invasion. As an underlying mechanism, Rab31 is presumed to act as a molecular switch between a more proliferative and an invasive phenotype. This prompted us to analyze whether Rab31 overexpression in breast cancer cells affects expression of genes involved in epithelial-to-mesenchymal transition (EMT)-like processes when compared to Rab31 low-expressing cells.

Methods
Commercially available profiler PCR arrays were applied to search for differentially expressed genes in Rab31 high- and low-expressing CAMA-1 breast cancer cells. Differential expression of selected candidate genes in response to Rab31 overexpression in CAMA-1 cells was validated by independent qPCR and protein assays.

Results
Gene expression profiling of key genes involved in EMT, or its reciprocal process MET, identified 9 genes being significantly up- or down-regulated in Rab31 overexpressing CAMA-1 cells, with the strongest effects seen for TGFB1, encoding TGF-ß1 (> 25-fold down-regulation in Rab31 overexpressing cells). Subsequent validation analyses by qPCR revealed a strong down-regulation of TGFB1 mRNA levels in response to increased Rab31 expression not only in CAMA-1 cells, but also in another breast cancer cell line, MDA-MB-231. Using ELISA and Western blot analysis, a considerable reduction of both intracellular and secreted TGF-ß1 antigen levels was determined in Rab31 overexpressing cells compared to vector control cells. Furthermore, reduced TGF-ß activity was observed upon Rab31 overexpression in CAMA-1 cells using a sensitive TGF-ß bioassay. Finally, the relationship between Rab31 expression and the TGF-ß axis was analyzed by another profiler PCR array focusing on genes involved in TGF-ß signaling. We found 12 out of 84 mRNAs significantly reduced and 7 mRNAs significantly increased upon Rab31 overexpression.

Conclusions
Our results demonstrate that Rab31 is a potent modulator of the expression of TGF-ß and other components of the TGF-ß signaling pathway in breast cancer cells.
Incidence and prevalence of violence toward health care workers in emergency departments: a multicenter cross-sectional survey
Authors: Alshahrani Mohammed , Alfaisal Razan , Alshahrani Khalid , Alotaibi Leyan , Alghoraibi Hissah , Alghamdi Eman , Almusallam Lulwah , Saffarini Zaineh , Alessa Salihah , Alwayel Faten , Saffarini Lubna , Alrawdhan Ali , Mapusao Charlene , Asonto Laila Perlas , Alsulaibikh Amal , Aljumaan Mohammed 
Published: December 2021

Abstract
Background
Workplace violence and abuse in the emergency department (ED) has increasingly become a serious and alarming phenomenon worldwide where health care professionals are more prone to violence compared with other specialties.

Aims
We aimed to estimate prevalence, and types of work place violence made against health care workers (HCW) in emergency departments of Arabian Gulf area.

Methods
We performed a descriptive cross-sectional study at several emergency departments in Saudi Arabia and United Arab Emirates wherein a previously validated questionnaire was distributed among health care workers. The survey consisted of 22 questions that assessed respondent’s workplace violence and/or abuse encounters, protective measures, available work place policies, and actions implemented to detect and deal with violence and abuse against healthcare providers. Descriptive statistics was used and P value < 0.05 was considered significant for all statistical tests performed.

Results
Seven hundred HCW in eleven emergency departments agreed to participate in the survey. Four hundred ninety-two completed the questionnaire with a response rate of 70%. More than 90% of the respondents were in the 20–39 years old bracket with an approximately equal gender distribution. Then, 20.9% of the respondents stated that they were physically attacked and 32.3% were attacked with a weapon. Most of the respondents (75.6%) reported that they were verbally abused or bullied by patients or relatives of patients. Staff responses to emotional abuse varied among respondents with the most frequent response of “told the person to stop” (22%), followed by “took no action” (19%). Further, 83.3% of respondents stated that there was an existing policy and procedure guidelines for reporting work place violence while 30.1% reported that they had not used any of these measures.

Conclusion
Workplace violence among HCW in the emergency departments are common in the Gulf area and can be serious in as far as use of weapons. Staff awareness focus on this under reported issue, and staff training to recognize and report potential aggression can predict a significant reduction of incidents.
Feasibility and efficacy of text messaging to promote care among trauma patients screened for HIV at an urban emergency department in Tanzania
Authors: Hyuha Gimbo M. , Sawe Hendry R. , Kilindimo Said , Mussa Raya Y. , Gulamhussein Masuma A. , Rwegoshora Shamila S. , Shayo Frida , Mdundo Winnie , Mfinanga Juma A. , Weber Ellen J. 
Published: December 2021

Abstract
Background
Due to the high prevalence of human immunodeficiency virus (HIV) in Tanzania, provider-initiated HIV testing for patients attending any health care setting is recommended. However, follow-up and linkage to care by those tested remain poor. We determined the feasibility and efficacy of text messaging to promote follow-up among otherwise healthy trauma patients who underwent provider-initiated HIV testing and counseling at an emergency department (ED) in Tanzania.

Material and methods
This randomized controlled trial (RCT) was conducted at Muhimbili National Hospital (MNH) ED between September 2019 and February 2020. Adult trauma patients consenting to HIV testing and follow-up text messaging were randomized to standard care (pre-test and post-test counseling) or standard care plus a series of three short message service (SMS) text message reminders for follow-up in an HIV clinic, if positive, or for retesting, if negative. Investigators blinded to the study assignment called participants 2 months after the ED visit if HIV-positive or 4 months if HIV-negative. We compared the proportion of people in the intervention and control groups completing recommended follow-up. Secondary outcomes were the proportion of patients agreeing to testing, proportion of patients agreeing to receiving text messages, and the proportion of HIV-positive and HIV-negative patients in each study arm who followed up.

Results
Of the 290 patients approached, 255 (87.9%) opted-in for testing and agreed to receive a text message. The median age of the study population was 29 [IQR 24–40] years. There were 127 patients randomized to the intervention group and 128 to the control group. The automated SMS system verified that 381 text messages in total were successfully sent. We traced 242 (94.9%) participants: 124 (51.2%) in the intervention group and 18 (488%) in the control group. A total of 100 (39.2%) subjects reported completing a follow-up visit, of which 77 (60.6%) were from the intervention group and 23 (17.9%) were from the control group (RR = 3.4, 95% CI 2.3–5.0). This resulted in a number needed to treat (NNT) of 2.3. Of the 246 HIV-negative participants, 37% underwent repeat screening: 59% of those in the intervention group and 16% in the control group (RR = 3.7, P = < 0.0001, NNT 2.3). Among the nine positive patients, all five in the intervention group and only three in the controls had follow-up visits.

Conclusion
Automated text message is a feasible and effective way to increase follow-up in HIV-tested individuals in a limited income country.
Effect of androgens on Sertoli cell maturation in human testis from birth to puberty
Authors: Lapoirie Marion , Dijoud Frederique , Lejeune Hervé , Plotton Ingrid 
Published: December 2021

AbstractBackgroundAndrogens are well known to be necessary for spermatogenesis. The purpose of this study was to determine Sertoli cell responsiveness to androgens according to age from birth to puberty.ResultsTesticular tissue samples were studied in a population of 84 control boys classified into seven groups according to age:group 1 (1–30 days), group 2 (1–3 months), group 3 (3–6 months), group 4 (0.5–3 years), group 5 (3–6 years), group 6 (6–12 years), and group 7 (12–16 years). We compared these data with those of 2 situations of pathology linked to androgens: 1/premature secretion of testosterone: 4 cases of Leydig cell tumor (LCT) in childhood; and 2 /defect of androgen receptors (AR): 4 cases of complete form of insensitivity to androgen syndrome (CAIS). In control boys, AR immunoreactivity (ir) in Sertoli cells appeared between 4.6 and 10.8 years of age, Anti-Mullerian Hormone (AMH) ir in Sertoli cells disappeared between 9.2 and 10.2 years of age. Connexin 43 (Cx43) ir in Sertoli cells and histological features of the onset of spermatogenesis appeared between 10.8 and 13,8 years of age. Cx43 ir was significantly higher in 12–16 year-olds than in younger boys. In case of CAIS, no spermatogenesis was observed, both AR and Cx43 ir were undetectable and AMH ir was elevated in Sertoli cells even at pubertal age. In the vicinity of LCTs, spermatogenesis occurred and both AR and Cx43 ir were strongly positive and AMH ir in Sertoli cells was low for age.ConclusionsAndrogen action on Sertoli cells is required for onset of spermatogenesis and premature androgen secretion by LCT can induce spermatogenesis in the vicinity of the tumor. AR ir appeared earlier than onset of spermatogenesis, with large interindividual variability. The timing and mechanisms of Sertoli cell responsiveness to androgens are important issues for understanding the induction of spermatogenesis at puberty.
gcMECM: graph clustering of mutual exclusivity of cancer mutations
Authors: Hu Ying , Yan Chunhua , Chen Qingrong , Meerzaman Daoud 
Published: December 2021

Abstract
Background
Next-generation sequencing platforms allow us to sequence millions of small fragments of DNA simultaneously, revolutionizing cancer research. Sequence analysis has revealed that cancer driver genes operate across multiple intricate pathways and networks with mutations often occurring in a mutually exclusive pattern. Currently, low-frequency mutations are understudied as cancer-relevant genes, especially in the context of networks.

Results
Here we describe a tool, gcMECM, that enables us to visualize the functionality of mutually exclusive genes in the subnetworks derived from mutation associations, gene–gene interactions, and graph clustering. These subnetworks have revealed crucial biological components in the canonical pathway, especially those mutated at low frequency. Examining the subnetwork, and not just the impact of a single gene, significantly increases the statistical power of clinical analysis and enables us to build models to better predict how and why cancer develops.

Conclusions
gcMECM uses a computationally efficient and scalable algorithm to identify subnetworks in a canonical pathway with mutually exclusive mutation patterns and distinct biological functions.
Effectiveness of joint 3 + 1 malaria strategy along China–Myanmar cross border areas
Authors: Lin Zu-rui , Li Shi-gang , Sun Xiao-dong , Guo Xiang-rui , Zheng Zhi , Yang Jie , Pian Hong-ru , Tian Peng , Chen Qi-yan , Sun Xiao-ying , Ding Chun-li , Duan Kai-xia , Chen Hong-wei , Bee Dakhidam Yaw , Zhou Hong-ning 
Published: December 2021

Abstract
Background
Cross-border malaria in Laiza City of Myanmar seriously affected Yingjiang County of China and compromised reaching the goal of malaria elimination by 2020. Since 2017, a pilot project on 3 + 1 strategy of joint cross-border malaria prevention and control was carried out for building a malaria buffer in these border areas. Here, 3 were the three preventive lines in China where different focalized approaches of malaria elimination were applied and + 1 was a defined border area in Myanmar where the integrated measures of malaria control were adopted.

Methods
A 5-year retrospective analysis (2015 to 2019) was conducted that included case detection, parasite prevalence and vector surveillance. Descriptive statistics was used and the incidence or rates were compared. The annual parasite incidence and the parasite prevalence rate in + 1 area of Myanmar, the annual importation rate in Yingjiang County of China and the density of An. minimus were statistically significant indictors to assess the effectiveness of the 3 + 1 strategy.

Results
In + 1 area of Myanmar from 2015 to 2019, the averaged annual parasite incidence was (59.11 ± 40.73)/1000 and Plasmodium vivax accounted for 96.27% of the total confirmed cases. After the pilot project, the annual parasite incidence dropped 89% from 104.77/1000 in 2016 to 12.18/1000 in 2019, the microscopic parasite prevalence rate dropped 100% from 0.34% in 2017 to zero in 2019 and the averaged density of An. Minimus per trap-night dropped 93% from 1.92 in June to 0.13 in September. The submicroscopic parasite prevalence rate increased from 1.15% in 2017 to 1.66% in 2019 without significant difference between the two surveys (P = 0.084). In Yingjiang County of China, neither indigenous nor introduced case was reported and 100% cases were imported from Myanmar since 2017. The averaged annual importation rate from 2015 to 2019 was (0.47 ± 0.15)/1000. After the pilot project, the annual importation rate dropped from 0.59/1000 in 2016 to 0.28/1000 in 2019 with an overall reduction of 53% in the whole county. The reduction was 67% (57.63/1000 to 18.01/1000) in the first preventive line, 52% (0.20/1000 to 0.10/1000) in the second preventive line and 36% (0.32/1000 to 0.22/1000) in the third preventive line. The averaged density of An. Minimus per trap-night in the first preventive line dropped 94% from 2.55 in June to 0.14 in September, without significant difference from that of + 1 area of Myanmar (Z value = − 1.18, P value = 0.24).

Conclusion
The pilot project on 3 + 1 strategy has been significantly effective in the study areas and a buffer zone of border malaria was successfully established between Laiza City of Myanmar and Yingjiang County of China.
Rare case of Proteus mirabilis native mitral valve endocarditis in an immunocompromised patient
Authors: Grossman Lindsay G. , Sharkey Joseph M. , Grossman David S. , Hartman Alan , Makaryus Mina , Shah Kaushal B. 
Published: December 2021

Abstract
Background
Bacterial infective endocarditis caused by Proteus mirabilis is rare and there are few cases in the literature. The natural history and treatment of this disease is not as clear but presumed to be associated with complicated urinary tract infection (cUTI).

Case presentation
A 65-year-old female with a history of rheumatoid arthritis, factor V Leiden hypercoagulability, and prior saddle pulmonary embolism presented to the emergency department following a mechanical fall. Computed Tomography showed evidence of acute/subacute splenic emboli. Complicated UTI was likely secondary to a ureteral stone. Blood and urine cultures also grew out P. mirabilis. Transthoracic echocardiography revealed a mobile echogenic density on the anterior mitral valve (MV) leaflet consistent with a vegetation. The patient underwent MV replacement, and P. mirabilis was isolated from the surgically removed valve.

Conclusions
We hypothesize that the patient’s immunocompromised status following steroid and Janus Kinase inhibitor usage for rheumatoid arthritis contributed to Gram-negative bacteremia following P. mirabilis UTI, ultimately seeding the native MV. Additional studies with larger numbers of Proteus endocarditis cases are needed to investigate an association between immunosuppression and Proteus species endocarditis.
Predisposing factors to acquisition of acute respiratory tract infections in the community: a systematic review and meta-analysis
Authors: Hammond Ashley , Halliday Alice , Thornton Hannah V. , Hay Alastair D. 
Published: December 2021

Abstract
Background
Preventing respiratory tract infections (RTIs) could have profound effects on quality of life, primary care workload, antibiotic prescribing and stewardship. We aimed to identify factors that increase and decrease RTI acquisition within Organisation for Economic Cooperation and Development (OECD) member countries.

Methods
Systematic search of Medline, Embase, Cochrane and ISI Web of Knowledge for studies conducted up to July 2020 reporting predisposing factors for community RTI acquisition. Pooled odds ratios were calculated using a random-effects model.

Results
23 studies investigated risk factors associated with community-acquired pneumonia (n = 15); any RTI (n = 4); influenza like illness (n = 2); and lower RTI (n = 2). Demographic, lifestyle and social factors were: underweight BMI (pooled odds ratio (ORp 2.14, 95% CI 1.58 to 2.70, p = 0.97); male sex (ORp 1.30, 95% CI 1.27 to 1.33, p = 0.66); contact with pets (ORp 1.35, 95% CI 1.16 to 1.54, p = 0.72); contact with children (ORp 1.35, 95% CI 1.15 to 1.56, p = 0.05); and ex-smoking status (ORp 1.57, 95% CI 1.26 to 1.88, p = 0.76). Health-related factors were: chronic liver condition (ORp 1.30, 95% CI 1.09 to 1.50, p = 0.34); chronic renal condition (ORp 1.47, 95% CI 1.09 to 1.85, p = 0.14); and any hospitalisation in previous five years (ORp 1.64, 95% CI 1.46 to 1.82, p = 0.66).

Conclusions
We identified several modifiable risk factors associated with increased likelihood of acquiring RTIs in the community, including low BMI, contact with children and pets. Modification of risk factors and increased awareness of vulnerable groups could reduce morbidity, mortality and antibiotic use associated with RTIs.

PROSPERO registration

CRD42019134176.