bluuebunny/crossref_metadata_2025 huggingface dataset:
Gain-of-function mutations in RPA1 cause a syndrome with short telomeres and somatic genetic rescue
Authors: Sharma Richa , Sahoo Sushree S. , Honda Masayoshi , Granger Sophie L. , Goodings Charnise , Sanchez Louis , Künstner Axel , Busch Hauke , Beier Fabian , Pruett-Miller Shondra M. , Valentine Marcus B. , Fernandez Alfonso G. , Chang Ti-Cheng , Géli Vincent , Churikov Dmitri , Hirschi Sandrine , Pastor Victor B. , Boerries Melanie , Lauten Melchior , Kelaidi Charikleia , Cooper Megan A. , Nicholas Sarah , Rosenfeld Jill A. , Polychronopoulou Sophia , Kannengiesser Caroline , Saintomé Carole , Niemeyer Charlotte M. , Revy Patrick , Wold Marc S. , Spies Maria , Erlacher Miriam , Coulon Stéphane , Wlodarski Marcin W.
Published: November 2021

Human telomere biology disorders (TBD)/short telomere syndromes (STS) are heterogeneous disorders caused by inherited loss-of-function mutations in telomere-associated genes. Here, we identify 3 germline heterozygous missense variants in the RPA1 gene in 4 unrelated probands presenting with short telomeres and varying clinical features of TBD/STS, including bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopenia, pulmonary fibrosis, or skin manifestations. All variants cluster to DNA-binding domain A of RPA1 protein. RPA1 is a single-strand DNA-binding protein required for DNA replication and repair and involved in telomere maintenance. We showed that RPA1E240K and RPA1V227A proteins exhibit increased binding to single-strand and telomeric DNA, implying a gain in DNA-binding function, whereas RPA1T270A has binding properties similar to wild-type protein. To study the mutational effect in a cellular system, CRISPR/Cas9 was used to knock-in the RPA1E240K mutation into healthy inducible pluripotent stem cells. This resulted in severe telomere shortening and impaired hematopoietic differentiation. Furthermore, in patients with RPA1E240K, we discovered somatic genetic rescue in hematopoietic cells due to an acquired truncating cis RPA1 mutation or a uniparental isodisomy 17p with loss of mutant allele, coinciding with stabilized blood counts. Using single-cell sequencing, the 2 somatic genetic rescue events were proven to be independently acquired in hematopoietic stem cells. In summary, we describe the first human disease caused by germline RPA1 variants in individuals with TBD/STS.
Genome-wide identification and expression profiling of Alba gene family members in response to abiotic stress in tomato (Solanum lycopersicum L.)
Authors: Wai Antt Htet , Cho Lae-Hyeon , Peng Xin , Waseem Muhammad , Lee Do-jin , Lee Je-Min , Kim Chang-Kil , Chung Mi-Young
Published: November 2021

Background

Alba (Acetylation lowers binding affinity) proteins are an ancient family of nucleic acid-binding proteins that function in gene regulation, RNA metabolism, mRNA translatability, developmental processes, and stress adaptation. However, comprehensive bioinformatics analysis on the Alba gene family of Solanum lycopersicum has not been reported previously.

Results

In the present study, we undertook the first comprehensive genome-wide characterization of the Alba gene family in tomato (Solanum lycopersicum L.). We identified eight tomato Alba genes, which were classified into two groups: genes containing a single Alba domain and genes with a generic Alba domain and RGG/RG repeat motifs. Cis-regulatory elements and target sites for miRNAs, which function in plant development and stress responses, were prevalent in SlAlba genes. To explore the structure-function relationships of tomato Alba proteins, we predicted their 3D structures, highlighting their likely interactions with several putative ligands. Confocal microscopy revealed that SlAlba–GFP fusion proteins were localized to the nucleus and cytoplasm, consistent with putative roles in various signalling cascades. Expression profiling revealed the differential expression patterns of most SlAlba genes across diverse organs. SlAlba1 and SlAlba2 were predominantly expressed in flowers, whereas SlAlba5 expression peaked in 1 cm-diameter fruits. The SlAlba genes were differentially expressed (up- or downregulated) in response to different abiotic stresses. All but one of these genes were induced by abscisic acid treatment, pointing to their possible regulatory roles in stress tolerance via an abscisic acid-dependent pathway. Furthermore, co-expression of SlAlba genes with multiple genes related to several metabolic pathways spotlighted their crucial roles in various biological processes and signalling.

Conclusions

Our characterization of SlAlba genes should facilitate the discovery of additional genes associated with organ and fruit development as well as abiotic stress adaptation in tomato.
The quality of patients’ self-blood pressure measurements: a cross-sectional study
Authors: Nessler Katarzyna , Krztoń-Królewiecka Anna , Suska Anna , Mann Mitchell R. , Nessler Michał B. , Windak Adam
Published: November 2021

Background

The accurate and independent measurement of blood pressure (BP) by patients is essential for home BP monitoring (HBPM) and determining the quality of hypertension (HTN) control. This study aimed to evaluate the BP self-measurement techniques of hypertensive patients and their accuracy in accordance with established guidelines. We sought to identify the common errors that patients make and suggest improvements that can be implemented in the primary healthcare setting to increase the reliability of HBPM conducted by hypertensive patients.

Methods

One hundred patients diagnosed with HTN completed a questionnaire inquiring about their health and demographic data and BP monitoring practices. Patients were then observed and filmed while measuring their BP on their own devices in five primary healthcare centres in Kraków, Poland. The correctness of their techniques was assessed in accordance with the European Society of Hypertension guidelines on HBPM.

Results

Only 3% of patients measured their BP without error; 60% made three or more errors. The most frequent error, made by 76% of subjects, was incorrect sphygmomanometer cuff placement (above or below heart level, or/and the indicator mark was not aligned with the brachial artery). Regarding patients’ previous instruction for the correct use of their devices, 36% of patients referred to their monitor’s user manual, 22% did not receive any prior assistance, and only 29% were adequately counselled by physicians on how to measure their BP correctly.

Conclusions

Our findings suggest that primary healthcare physicians and their personnel often do not adequately instruct patients on how to measure their BP correctly. Therefore, healthcare systems must provide patients with more adequate training and reference materials on the best practices of BP monitoring.
Clinical outcomes in 2481 unselected real-world patients treated with a polymer-free sirolimus-eluting stent: 3 years results from the NANO multicenter Registry
Authors: Dai Yi , Wang Rutao , Chen Fengying , Zhang Yaojun , Liu Yi , Huang He , Yang Ping , Zhang Ruining , Zheng Bo , Gao Chao , Chen Yundai , Tao Ling
Published: November 2021

Objectives

To evaluate the 3-year clinical outcomes of a polymer-free sirolimus-eluting, Nano plus stent for the treatment of coronary artery disease in the NANO multicenter Registry.

Background

The long-term clinical data evaluating the safety and efficacy of the novel polymer-free sirolimus-eluting Nano plus stent (Lepu Medical, Beijing, China) is limited.

Methods

The NANO all-comers Registry trial was a prospective, multicenter clinical registry conducted in 26 centers in China between August 2016 and January 2017. A total of 2481 consecutive patients were exclusively treated with the Nano plus stent. The primary clinical endpoint, target lesion failure (TLF, defined as cardiac death, target vessel nonfatal myocardial infarction, and clinically driven target lesion revascularization [CD-TLR]), was analyzed at 3 years.

Results

At 3 years, 2295 patients (92.5%) were followed. The incidence of TLF was 6.8% (168/2481). The rate of cardiac death was 3.8% (94/2481), target vessel nonfatal myocardial infarction 0.7% (18/2481), and CD-TLR 2.9% (68/2481). The rate of definite/probable stent thrombosis was 0.5% (13/2481). The risk factors of diabetes mellitus, acute myocardial infarction, age, chronic renal failure, in-stent restenosis, chronic total occlusion, and left ventricular ejection fraction < 40% were the independent predictors of 3-year TLF.

Conclusions

At three years, the rate of TLF was relatively low in patients treated with the polymer-free Nano plus stent. The polymer-free Nano plus stent showed a favorable safety and efficacy profile in real-world patients.

Clinical trial registrationURL:https://www.clinicaltrials.gov/. Unique identifier: NCT02929030.
Strategies for working across Canadian practice-based research and learning networks (PBRLNs) in primary care: focus on frailty
Authors: Thandi Manpreet , Wong Sabrina T. , Aponte-Hao Sylvia , Grandy Mathew , Mangin Dee , Singer Alexander , Williamson Tyler
Published: November 2021

Background

Practice based research and learning networks (PBRLNs) are groups of learning communities that focus on improving delivery and quality of care. Accurate data from primary care electronic medical records (EMRs) is crucial in forming the backbone for PBRLNs. The purpose of this work is to: (1) report on descriptive findings from recent frailty work, (2) describe strategies for working across PBRLNs in primary care, and (3) provide lessons learned for engaging PBRLNs.

Methods

We carried out a participatory based descriptive study that engaged five different PBRLNs. We collected Clinical Frailty Scale scores from a sample of participating physicians within each PBRLN. Descriptive statistics were used to analyze frailty scores and patients’ associated risk factors and demographics. We used the Consolidated Framework for Implementation Research to inform thematic analysis of qualitative data (meeting minutes, notes, and conversations with co-investigators of each network) in recognizing challenges of working across networks.

Results

One hundred nine physicians participated in collecting CFS scores across the five provinces (n = 5466). Percentages of frail (11-17%) and not frail (82-91%) patients were similar in all networks, except Ontario who had a higher percentage of frail patients (25%). The majority of frail patients were female (65%) and had a significantly higher prevalence of hypertension, dementia, and depression. Frail patients had more prescribed medications and numbers of healthcare encounters. There were several noteworthy challenges experienced throughout the research process related to differences across provinces in the areas of: numbers of stakeholders/staff involved and thus levels of burden, recruitment strategies, data collection strategies, enhancing engagement, and timelines.

Discussion

Lessons learned throughout this multi-jurisdictional work included: the need for continuity in ethics, regular team meetings, enhancing levels of engagement with stakeholders, the need for structural support and recognizing differences in data sharing across provinces.

Conclusion

The differences noted across CPCSSN networks in our frailty study highlight the challenges of multi-jurisdictional work across provinces and the need for consistent and collaborative healthcare planning efforts.
Assessment of the health status of middle-aged and elderly men with head scale, SF-36, IIEF5, AMS, and IPSS
Authors: Zhu Yi , Li Jian-Hui , Zhao Jing , Zheng Jun-Biao , Liang Qun-Feng , Yu Xiao-Hua , Zhang Shu-Cheng , Shi Hui-Juan , Zhou Wei-Jin , Zhu Qian-Xi
Published: November 2021

Background

Identifying practical and distinguished indicators and influencing factors of male aging may be useful in predicting subsequent aging trends, designing personalized prevention, and improving lifestyle and health.

Methods

A cross-sectional, population-based study was performed in Jiashan County, China in 2016. A total of 690 local male residents, aged 40 to 80 years, were eligible for recruitment. Demographic and lifestyle information was collected through structured interviews. A self-designed head scale, the Medical Outcomes Study 36-item Short Form (SF-36), International Index of Erectile Function (IIEF5), Aging Males’ Symptoms (AMS), and International Prostate Symptom Score (IPSS) were used. Analysis of variance, local polynomial regression smoothing curves, multiple linear regression, and partial correlation analyses were performed.

Results

All the scales deteriorated with increasing age (P < 0.01), especially from the age of 60. The most significant changes between adjacent age groups were found in IIEF5 scores (16.7, 43.5 and 39.4%). Income, nutrition, personality and neighborhood relationship had an effect on SF-36 and AMS after adjusting for age (P < 0.01). Furthermore, neighborhood relationship modified the age effect on the head scale score and IIEF5 (P = 0.03); nutrition modified the relationship between age and SF-36 (P < 0.01).

Conclusions

Recession of reproductive health may be a distinct predictor of male aging. The associations of social inequalities or personality and health offer potential interventions for men’s health in aging. Self-reported scales may limit the precision and more physical fitness tests could be combined for a more precise assessment.
Survey of pretreatment HIV drug resistance and the genetic transmission networks among HIV-positive individuals in southwestern China, 2014–2020
Authors: Xu Xiaoshan , Luo Liuhong , Song Chang , Li Jianjun , Chen Huanhuan , Zhu Qiuying , Lan Guanghua , Liang Shujia , Shen Zhiyong , Cao Zhiqiang , Feng Yi , Liao Lingjie , Xing Hui , Shao Yiming , Ruan Yuhua
Published: November 2021

Background

Pretreatment drug resistance (PDR) can limit the effectiveness of HIV antiretroviral therapy (ART). The aim of this study was to assess the prevalence of PDR among HIV-positive individuals that initiated antiretroviral therapy in 2014–2020 in southwestern China.

Methods

Consecutive cross-sectional surveys were conducted in Qinzhou, Guangxi. We obtained blood samples from individuals who were newly diagnosed with HIV in 2014–2020. PDR and genetic networks analyses were performed by HIV-1 pol sequences using the Stanford HIV-database algorithm and HIV-TRACE, respectively. Univariate and multivariate logistic regression models were used to explore the potential factors associated with PDR.

Results

In total, 3236 eligible HIV-positive individuals were included. The overall prevalence of PDR was 6.0% (194/3236). The PDR frequency to NNRTI (3.3%) was much higher than that of NRTI (1.7%, p < 0.001) and PI (1.2%, p < 0.001). A multivariate logistic regression analysis revealed that PDR was significantly higher among individuals aged 18–29 (adjusted odds ratio (aOR): 1.79, 95% CI 1.28–2.50) or 30–49 (aOR: 2.82, 95% CI 1.73–4.82), and harboring CRF08_BC (aOR: 3.23, 95% CI 1.58–6.59). A total of 1429 (43.8%) sequences were linked forming transmission clusters ranging in size from 2 to 119 individuals. Twenty-two individuals in 10 clusters had the same drug resistant mutations (DRMs), mostly to NNRTIs (50%, 5/10).

Conclusions

The overall prevalence of PDR was medium, numerous cases of the same DRMs among genetically linked individuals in networks further illustrated the importance of surveillance studies for mitigating PDR.
Relationship between malnutrition and possible sarcopenia in the AWGS 2019 consensus affecting mortality in hemodialysis patients: a prospective cohort study
Authors: Kono Kenichi , Moriyama Yoshifumi , Yabe Hiroki , Hara Ayaka , Ishida Takeki , Yamada Tetsuya , Nishida Yusuke
Published: November 2021

Background

The first objective of this study was to determine the relationship between muscle strength or physical performance and mortality, and the second objective was to show the relationship of Geriatric Nutritional Risk Index (GNRI) to muscle strength and physical performance decline.

Methods

We examined handgrip, the 5-times chair stand test, and GNRI in 635 maintenance hemodialysis patients and followed up for 72 months. Predictors for all-cause death were examined using Kaplan-Meier analysis and Cox proportional analysis. The relationship between possible sarcopenia and nutritional disorder (GNRI) was constructed receiver operating characteristic (ROC) curve. We used the Youden index to determine the optimal cutoff points for GNRI.

Results

The multivariate Cox proportional hazard analysis revealed that the GNRI did not show any significance, although handgrip (HR 3.61, 95% CI 1.70–7.68, p < 0.001) and the 5-times chair stand test (HR 1.71 95% CI 1.01–2.90, p = 0.045) were significant predictors for mortality. On the evaluation of possible sarcopenia by handgrip strength, the area under curve (AUC) on ROC curve analysis were 0.68 (95% CI 0.64–0.72), and 5-chair stand, the AUC on ROC were 0.55 (95% CI 0.51–0.60). The cut-off value for the GNRI discriminating those at possible sarcopenia by handgrip strength based on the Youden index was 91.5.

Conclusions

Our study suggests that the handgrip strength test of the AWGS 2019 sarcopenia consensus was a simple and useful tool to predict mortality in chronic hemodialysis patients. Furthermore, GNRI assessment can be a useful tool for screening before assessing possible sarcopenia when it is difficult to perform SARC-F to all patients.
‘Asking for help’: a qualitative interview study exploring the experiences of interpersonal counselling (IPC) compared to low-intensity cognitive behavioural therapy (CBT) for women with depression during pregnancy
Authors: Ingram Jenny , Johnson Debbie , O’Mahen Heather A. , Law Roslyn , Culpin Iryna , Kessler David , Beasant Lucy , Evans Jonathan
Published: November 2021

Background

Treating depression early in pregnancy can improve health outcomes for women and their children. Current low-intensity psychological therapy for perinatal depression is a supported self-help approach informed by cognitive behavioural therapy (CBT) principles. Interpersonal counselling (IPC) may be a more appropriate low-intensity talking therapy for addressing the problems experienced by pregnant women with depression. A randomised feasibility trial (ADAGIO) has compared the acceptability of offering IPC for mild-moderate antenatal depression in routine NHS services compared to low-intensity CBT. This paper reports on a nested qualitative study which explored women’s views and expectations of therapy, experiences of receiving IPC, and Psychological Wellbeing Practitioners (PWPs - junior mental health workers) views of delivering the low-intensity therapy.

Methods

A qualitative study design using in-depth semi-structured interviews and focus groups. Thirty-two pregnant women received talking therapy within the ADAGIO trial; 19 contributed to the interview study from July 2019 to January 2020; 12 who had IPC and seven who had CBT. All six PWPs trained in IPC took part in a focus group or interview. Interviews and focus groups were recorded, transcribed, anonymised, and analysed using thematic methods.

Results

Pregnant women welcomed being asked about their mental health in pregnancy and having the chance to have support in accessing therapy. The IPC approach helped women to identify triggers for depression and explored relationships using strategies such as ‘promoting self-awareness through mood timelines’, ‘identifying their circles of support’, ‘developing communication skills and reciprocity in relationships’, and ‘asking for help’. PWPs compared how IPC differed from their prior experiences of delivering low-intensity CBT. They reported that IPC included a useful additional emotional component which was relevant to the perinatal period.

Conclusions

Identifying and treating depression in pregnancy is important for the future health of both mother and child. Low-intensity perinatal-specific talking therapies delivered by psychological wellbeing practitioners in routine NHS primary care services in England are acceptable to pregnant women with mild-moderate depression. The strategies used in IPC to manage depression, including identifying triggers for low mood, and communicating the need for help, may be particularly appropriate for the perinatal period.

Trial registration

ISRCTN 11513120. 02/05/2019.
Identification of key genes and pathways associated with resting mast cells in meningioma
Authors: Xie Hui , Yuan Ce , Ding Xiao-hui , Li Jin-jiang , Li Zhao-yang , Lu Wei-cheng
Published: November 2021

Background

To identify candidate key genes and pathways related to resting mast cells in meningioma and the underlying molecular mechanisms of meningioma.

Methods

Gene expression profiles of the used microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. GO and KEGG pathway enrichments of DEGs were analyzed using the ClusterProfiler package in R. The protein-protein interaction network (PPI), and TF-miRNA- mRNA co-expression networks were constructed. Further, the difference in immune infiltration was investigated using the CIBERSORT algorithm.

Results

A total of 1499 DEGs were identified between tumor and normal controls. The analysis of the immune cell infiltration landscape showed that the probability of distribution of memory B cells, regulatory T cells (Tregs), and resting mast cells in tumor samples were significantly higher than those in the controls. Moreover, through WGCNA analysis, the module related to resting mast cells contained 158 DEGs, and KEGG pathway analysis revealed that the DEGs were dominant in the TNF signaling pathway, cytokine-cytokine receptor interaction, and IL-17 signaling pathway. Survival analysis of hub genes related to resting mast cells showed that the risk model was constructed based on 9 key genes. The TF-miRNA- mRNA co-regulation network, including MYC-miR-145-5p, TNFAIP3-miR-29c-3p, and TNFAIP3-hsa-miR-335-3p, were obtained. Further, 36 nodes and 197 interactions in the PPI network were identified.

Conclusion

The results of this study revealed candidate key genes, miRNAs, and pathways related to resting mast cells involved in meningioma development, providing potential therapeutic targets for meningioma treatment.
Identification of tumour immune microenvironment-related alternative splicing events for the prognostication of pancreatic adenocarcinoma
Authors: Chen Bo , Deng Tuo , Deng Liming , Yu Haitao , He Bangjie , Chen Kaiyu , Zheng Chongming , Wang Daojie , Wang Yi , Chen Gang
Published: November 2021

Purpose

Pancreatic adenocarcinoma (PAAD) is characterized by low antitumour immune cell infiltration in an immunosuppressive microenvironment. This study aimed to systematically explore the impact on prognostic alternative splicing events (ASs) of tumour immune microenvironment (TIME) in PAAD.

Methods

The ESTIMATE algorithm was implemented to compute the stromal/immune-related scores of each PAAD patient, followed by Kaplan–Meier (KM) survival analysis of patients with different scores grouped by X-tile software. TIME-related differentially expressed ASs (DEASs) were determined and evaluated through functional annotation analysis. In addition, Cox analyses were implemented to construct a TIME-related signature and an AS clinical nomogram. Moreover, comprehensive analyses, including gene set enrichment analysis (GSEA), immune infiltration, immune checkpoint gene expression, and tumour mutation were performed between the two risk groups to understand the potential mechanisms. Finally, Cytoscape was implemented to illuminate the AS-splicing factor (SF) regulatory network.

Results

A total of 437 TIME-related DEASs significantly related to PAAD tumorigenesis and the formation of the TIME were identified. Additionally, a robust TIME-related prognostic signature based on seven DEASs was generated, and an AS clinical nomogram combining the signature and four clinical predictors also exhibited prominent discrimination by ROC (0.762 ~ 0.804) and calibration curves. More importantly, the fractions of CD8 T cells, regulatory T cells and activated memory CD4 T cells were lower, and the expression of four immune checkpoints—PD-L1, CD47, CD276, and PVR—was obviously higher in high-risk patients. Finally, functional analysis and tumour mutations revealed that aberrant immune signatures and activated carcinogenic pathways in high-risk patients may be the cause of the poor prognosis.

Conclusion

We extracted a list of DEASs associated with the TIME through the ESTIMATE algorithm and constructed a prognostic signature on the basis of seven DEASs to predict the prognosis of PAAD patients, which may guide advanced decision-making for personalized precision intervention.
Desistance from crime following substance use treatment: the role of treatment retention, social network and self-control
Authors: Skjærvø Ingeborg , Clausen Thomas , Skurtveit Svetlana , Bukten Anne
Published: November 2021

Background

Reductions in crime are often reported following substance use treatment. We explore the relationship between desistance from crime, treatment type, treatment retention and positive changes in known risk factors for crime.

Methods

We used data from the NorComt-study; a longitudinal study of substance users (n = 341) enrolled in comprehensive treatment in Norway (2012–2015). At treatment initiation (T0) and 1 year later (T1), we collected self-reported data on criminal involvement, treatment, substance use, social network and self-control. We calculated adjusted odds ratios (aOR) and 95% confidence intervals (CI) with multinomial logistic regression analysis.

Results

Overall, 1 year following treatment initiation 69% reported desistance from crime, 18% reported continued crime and 12% reported no crime at all in the study period. Desistance was high for OMT patients in ongoing treatment (79% desisted) and for inpatients regardless of treatment status (79–93% desisted), while not as high among OMT patients with interrupted treatment (47% desisted). For participants that continued crime during follow-up, the average number of criminal acts per month was reduced (p < 0.001). Desistance at follow-up was associated with being older (aOR: 1.05, CI: 1.00–1.10), inpatient treatment (aOR: 3.71, CI: 1.12–12.29), being in ongoing treatment (inpatient or OMT) (aOR: 2.90, CI: 1.01–8.36), having no stimulant use in the study period (aOR: 4.86, CI: 1.72–13.70), leaving a substance using social network (aOR 2.87, CI: 1.15–7.18) and improvement in self-control score (aOR: 1.08, CI: 1.04–1.13).

Conclusions

Retention in treatment is particularly important for crime outcomes among OMT patients. Positive changes in social network and self-control are potential contributors to desistance from crime. Targeted interventions towards crime reduction are recommended for patients with stimulant use, which appears to be a persistent risk factor for crime over time.
Burnout and peritraumatic distress of healthcare workers in the COVID-19 pandemic
Authors: Jang Yeonhoon , You Myoungsoon , Lee Heeyoung , Lee Minjung , Lee Yeji , Han Jin-Ok , Oh Jeong Hyeon
Published: November 2021

Background

To evaluate the current status of emotional exhaustion and peritraumatic distress of healthcare workers (HCWs) in the COVID-19 pandemic, and identify factors associated with their mental health status.

Methods

An online survey involving 1068 of consented HCWs that included nurses, physicians, and public health officers was conducted in May 2020. Descriptive statistics and multivariate regression analyses were performed on the collected data.

Results

Although no significant difference in peritraumatic distress was observed among the surveyed HCWs, the workers’ experience of emotional exhaustion varied according to work characteristics. Respondents who were female, older, living with a spouse, and/or full-time workers reported higher levels of emotional exhaustion. Public health officers and other medical personnel who did not have direct contact with confirmed patients and full-time workers had a higher level of peritraumatic distress. Forced involvement in work related to COVID-19, worry about stigma, worry about becoming infected, and perceived sufficiency of organizational support negatively predict emotional exhaustion and peritraumatic distress.

Conclusions

Job-related and emotional stress of HCWs should not be neglected. Evidence-based interventions and supports are required to protect HCWs from mental illness and to promote mental health of those involved in the response to the COVID-19 pandemic.
Retroperitoneoscopic lumbar sympathectomy for the treatment of primary plantar hyperhidrosis
Authors: Hur Kyung Jae , Moon Hyong Woo , Park Yong Hyun , Bae Woong Jin , Cho Hyuk Jin , Ha U-Syn , Lee Ji Youl , Kim Sae Woong , Hong Sung-Hoo
Published: November 2021

Background

Primary plantar hyperhidrosis (PPH) is an idiopathic disease, characterized by excessive sweating of the feet. It leads to significant disturbance in private and professional daily lifestyle, due to excessive sweating. The aim of this study is to present the safety, efficacy and procedures of retroperitoneoscopic lumbar sympathectomy (RLS) for treatment of PPH.

Methods

RLS was performed 60 times in 30 patients (18 men, 12 women) with PPH in our institution from May 2019 to October 2020. All procedures were carried out by laparoscopy with retroperitoneal approach. Clinical data including patient demographics and perioperative, postoperative outcomes were evaluated. Recurrence of symptoms, and any adverse effects of surgery were evaluated after 7 to 30 days in outpatient clinic, and thereafter every 6 months.

Results

Mean age of patients was 33.6 (± standard deviation 10.8) years. Fourteen and fifteen patients were previously treated with medical therapy or endoscopic thoracic sympathectomy (ETS) respectively. Mean preoperative quality of life (QoL) score of patients was 91.8 (VERY BAD), but postoperative 12 months (QoL) score decreased to 29.1 (MUCH BETTER). There was no serious postoperative complication. During the mean 22 months of follow-up period, no compensatory sweating was observed.

Conclusions

RLS can be a safe and effective surgical treatment for severe PPH, especially for the patients with persistent plantar sweating even after conservative management and ETS. RLS also could be offered to surgeons who are familiar with retroperitoneal space anatomy as feasible surgical treatment for PPH.
Effects of platelet concentrates on implant stability and marginal bone loss: a systematic review and meta-analysis
Authors: Qu Changxing , Luo Feng , Hong Guang , Wan Qianbing
Published: November 2021

Background

Osseointegration is essential for the success and stability of implants. Platelet concentrates were reported to enhance osseointegration and improve implant stability. The purpose of this review is to systematically analyze the effects of platelet concentrates on implant stability and marginal bone loss.

Methods

Two researchers independently performed searches in the following databases (last searched on 21 July 2021): MEDLINE (PubMed), Cochrane Library, EMBASE, and Web of Science. In addition, a manual search was carried out on references of relevant reviews and initially included studies. All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on the application of platelet concentrates in the implant surgery procedure were included. The risk of bias of RCTs and CCTs were assessed with a revised Cochrane risk of bias tool for randomized trials (RoB 2.0) and the risk of bias in non-randomized studies—of interventions (ROBINS-I) tool, respectively. Meta-analyses on implant stability and marginal bone loss were conducted. Researchers used mean difference or standardized mean difference as the effect size and calculated the 95% confidence interval. In addition, subgroup analysis was performed based on the following factors: type of platelet concentrates, method of application, and study design.

Results

Fourteen studies with 284 participants and 588 implants were included in the final analysis. 11 studies reported implant stability and 5 studies reported marginal bone level or marginal bone loss. 3 studies had high risk of bias. The meta-analysis results showed that platelet concentrates can significantly increase implant stability at 1 week (6 studies, 302 implants, MD 4.26, 95% CI 2.03–6.49, P < 0.001) and 4 weeks (8 studies, 373 implants, MD 0.67, 95% CI 0.46–0.88, P < 0.001) after insertion, significantly reduced marginal bone loss at 3 months after insertion (4 studies, 95 implants, mesial: MD − 0.33, 95% CI − 0.46 to − 0.20, P < 0.001; distal: MD − 0.38, 95% CI − 0.54 to − 0.22, P < 0.001). However, the improvement of implant stability at 12 weeks after insertion was limited (P = 0.10). Subgroup analysis showed that PRP did not significantly improve implant stability at 1 week and 4 weeks after insertion (P = 0.38, P = 0.17). Platelet concentrates only placed in the implant sites did not significantly improve implant stability at 1 week after insertion (P = 0.20).

Conclusions

Platelet concentrates can significantly improve implant stability and reduce marginal bone loss in the short term. Large-scale studies with long follow‐up periods are required to explore their long-term effects and compare effects of different types.

Trial registration

This study was registered on PROSPERO, with the Registration Number being CRD42021270214.
Pipelle endometrial biopsy for abnormal uterine bleeding: do patient’s pain and anxiety really impact on sampling success rate?
Authors: Kaiyrlykyzy Aiym , Linkov Faina , Foster Faye , Bapayeva Gauri , Ukybassova Talshyn , Aimagambetova Gulzhanat , Kenbayeva Kamila , Ibrayimov Bakytkali , Lyasova Alla , Terzic Milan
Published: November 2021

Background

Pipelle endometrial biopsy is vital for the early diagnostics of endometrial pathology and is performed in outpatient setting in minimally invasive manner. One of the reported disadvantages of sampling with Pipelle curette is failure to collect enough tissue for histological analysis. The role of psychological factors such as anxiety and pain sensitivity in obtaining adequate samples is not well known. The study's objective was to explore whether there is relationship between severe pain, anxiety, and the rate of Pipelle failure.

Methods

Study included 158 women with median age of 42 who underwent Pipelle endometrial biopsy at Clinical Academic Department of Women’s Health of the University Medical Center (UMC), Nur-Sultan City, Kazakhstan with an abnormal uterine bleeding from June 2019 to April 2021. Women were asked to fill survey on pain, anxiety before, during and after the procedure.

Results

3.8%, 15.19% and 4.43% of women reported severe pain and 39.24%, 34.18% and 14.56% of women reported severe anxiety prior, during and after procedure, respectively. Women who experienced severe pain during procedure tend to be more anxious during procedure (p = 0.0001) and have higher number of sampling attempts (p = 0.0040). Pain level was higher among patients sampled by the junior OB/GYN specialist (p < 0.0001). We found no differences in Pipelle biopsy success rates in relationship to baseline, during and postprocedural pain and anxiety scores.

Conclusion

Anxiety during procedure performance was significantly associated with severe pain during the procedure but did not represent a key element for the success of Pipelle biopsy.
A primer of an in-depth resilience status for German medical graduates: results of a cross-sectional survey on the status quo of resilience among graduates of human medicine in Bavaria, Germany - a necessary step in building an emotionally equipped healthcare work-force
Authors: Kiesewetter J. , Huber J.
Published: November 2021

Background

Resilience is a widely-used catchword in the last couple of years to describe the resistance to psychological strains of life, especially for the healthcare work-force. The promises of resilience to burnout sound great and what we all would want: less health impairment despite stress, higher work satisfaction and last but not least higher work performance. There is research that shows that students and physicians have high emotional distress and low resilience, yet comparably little is known which aspects of resilience are exactly impaired in the upcoming work-force. With our study we investigated the in-depth resilience status of medical graduates from five medical schools within their first year after graduation. In this, additionally to assessing the resilience status as a whole we investigate the answers on the singular items and the relationship of the resilience status with neighboring constructs.

Methods

In 2018, 1610 human medical graduates from five Bavarian medical schools were asked to take part at cross-sectional Bavarian graduate survey (Bayerische Absolventenstudie Medizin, MediBAS). The response rate was 38,07, 60% of the participants were female. For the identification of the in-depth resilience status we included the 5-point Likert 10-Item Connor-Davidson Resilience Scale, German Version in a graduate survey posted to 5 medical schools and over 1610 eligible participants of whom 610 (60% female) filled out at least parts of the survey. To identify relationships to other aspects we posed further questionnaires.

Results

The resilience status showed a mean resilience score of M = 37.1 (SD = 6.30). The score ranges from 3.22 (I am not easily discouraged by failure) to 4.26 (I am able to adapt to change). One third of the participants chose not to answer the item “I am able to handle unpleasant feeling”. Relationships to job satisfaction, scientific competence and stress are presented in the article.

Conclusions

The study shows that the overall resilience status of medical graduates one year after their graduation is rather high, but subjectively they do not feel equivalently resilient for the different aspects they face in their job. Especially, how to handle their emotions seems to be challenging for some of the young physicians. In the article we sketch ideas how to handle the specific training needs the study has identified.
“I haven’t had to bare my soul but now I kind of have to”: describing how voluntary assisted dying conscientious objectors anticipated approaching conversations with patients in Victoria, Australia
Authors: Haining Casey Michelle , Keogh Louise Anne
Published: November 2021

Background

Dealing with end of life is challenging for patients and health professionals alike. The situation becomes even more challenging when a patient requests a legally permitted medical service that a health professional is unable to provide due to a conflict of conscience. Such a scenario arises when Victorian health professionals, with a conscientious objection (CO) to voluntary assisted dying (VAD), are presented with patients who request VAD or merely ask about VAD. The Voluntary Assisted Dying Act 2017 (Vic) recognizes the inherent conflict of conscience that may arise for some health professionals when asked to provide VAD and responds by affording broad protection to conscientious objectors who wish to refuse to take part in the VAD process.

Methods

Seventeen semi-structured qualitative interviews were conducted with Victorian health professionals with a self-identified CO to VAD in the lead-up to the implementation of VAD in Victoria. Interviews explored how participants anticipated they would manage their CO in practice. Interviews were transcribed verbatim and analyzed thematically.

Results

Our results reveal that the way in which health professionals claimed they would approach CO conversations is variable and was dependant on the strength of their opposition to VAD. We categorized conscientious objectors according to their approach as either dissuasive non-referrers, passive non-referrers, facilitators or negotiators. Our study also explores the perceived difficulties of exercising one’s CO as identified by our participants.

Conclusion

The broad protection offered by the Voluntary Assisted Dying Act 2017 (Vic) encourages a range of behaviors from conscientious objectors, due to the minimal obligations imposed. In order to assist conscientious objectors, more policy, institutional guidance, and education needs to be available to conscientious objectors explicitly addressing how to effectively manage one’s CO. Such guidance is imperative to ensuring that their moral integrity is preserved and that they are exercising their CO appropriately.
The Swedish translation and cultural adaptation of the Measure of Moral Distress for Healthcare Professionals (MMD-HP)
Authors: Fischer-Grönlund Catarina , Brännström Margareta
Published: November 2021

Background

Moral distress has been described as an emotionally draining condition caused by being prevented from providing care according to one’s convictions. Studies have described the impact of moral distress on healthcare professionals, their situations and experiences. The Measure of Moral Distress for Healthcare Professionals (MMD-HP) is a questionnaire that measures moral distress experienced by healthcare professionals at three levels: patient, system and team. The aim of this project was to translate and make a cultural adaption of the MMD -HP to the Swedish context.

Methods

The questionnaire comprises 27 items, rated according to frequency and intensity on a five-point Likert scale (0–4). The procedure for translating MMD-HP followed WHO guidelines (2020). These entailed a forward translation from English to Swedish, a back translation, expert panel validation, pretesting and cognitive face-to-face interviews with 10 healthcare professionals from various professions and healthcare contexts.

Results

The Swedish version of MMD-HP corresponds essentially to the concept of the original version. Parts of some items’ had to be adjusted or removed in order to make the item relevant and comprehensible in a Swedish context. Overall, the cognitive interviewees recognized the content of the items which generally seemed relevant and comprehensible.

Conclusion

The Swedish version of MMD-HP could be a useful tool for measuring moral distress among healthcare professionals in a Swedish healthcare context.
Tube-dwelling in early animals exemplified by Cambrian scalidophoran worms
Authors: Wang Deng , Vannier Jean , Aria Cédric , Sun Jie , Han Jian
Published: November 2021

Background

The radiation of ecdysozoans (moulting animals) during the Cambrian gave rise to panarthropods and various groups of worms including scalidophorans, which played an important role in the elaboration of early marine ecosystems. Although most scalidophorans were infaunal burrowers travelling through soft sediment at the bottom of the sea,Selkirkialived inside a tube.

Results

We explore the palaeobiology of these tubicolous worms, and more generally the origin and evolutionary significance of tube-dwelling in early animals, based on exceptionally preserved fossils from the early Cambrian Chengjiang Lagerstätte (Stage 3, China) including a new species,Selkirkia transitasp. nov. We find that the best phylogenetic model resolvesSelkirkiaas a stem-group priapulid.Selkirkiasecreted a protective cuticular thickening, the tube, inside which it was able to move during at least part of its life. Partly based on measured growth patterns, we construe that this tube was separated from the trunk during a moulting process that has no direct equivalent in other scalidophorans. Although the ontogeny ofSelkirkiais currently unknown, we hypothesize that its conical tube might have had the same ecological function and possibly even deep development origin as the lorica, a protective cuticular thickening found in larval priapulids and adult loriciferans.Selkirkiais seen as a semi-sedentary animal capable of very shallow incursions below the water/sediment interface, possibly for feeding or during the tube-secreting phase. Brachiopod epibionts previously reported from the Xiaoshiba Lagerstätte (ca. 514 Ma) also presumably occur inSelkirkia sinicafrom Chengjiang (ca. 518 Ma).

Conclusions

Our critical and model-based approach provides a new phylogenetic framework for Scalidophora, upon which to improve in order to study the evolution of morphological characters in this group. Tube-dwelling is likely to have offeredSelkirkiabetter protection and anchoring to sediment and has developed simultaneously in other Cambrian animals such as hemichordates, annelids or panarthropods. Often lost in modern representatives in favour of active infaunal lifestyles, tube-dwelling can be regarded as an early evolutionary response of various metazoans to increasing environmental and biological pressure in Cambrian marine ecosystems.
Impact of cumulative cisplatin dose in childhood nasopharyngeal carcinoma based on neoadjuvant chemotherapy response in the intensity-modulated radiotherapy era: a real-world study
Authors: Jin Ya-Nan , Qiang Meng-Yun , Liu Meng-Meng , Cheng Zhi-Bin , Zhang Wang-Jian , Ryan Ian , Marks Tia , Yao Ji-Jin , Xia Liang-Ping
Published: November 2021

Background

We aimed to comprehensively investigate the optimal cumulative cisplatin dose during concurrent chemoradiotherapy (CC-CCD) for locoregionally advanced nasopharyngeal carcinoma (CA-LANPC) with different tumor responses after neoadjuvant chemotherapy (NAC).

Methods

Patients with CA-LANPC who underwent NAC followed by cisplatin-based concurrent chemoradiotherapy were retrospectively analyzed. Evaluation of tumor response in patients was conducted by Response Evaluation Criteria for Solid Tumor (RECIST) 1.1 after two to four cycles NAC. Multivariate Cox proportional hazards models were used for prognosis. Recursive partitioning analysis (RPA) was conducted to classify participates and predict disease-free survival (DFS).

Results

One hundred and thirty-two patients with favorable response after NAC were included. The median CC-CCD was 163 mg/m2 (IQR, 145–194 mg/m2), and 160 mg/m2 was selected as the cutoff point to group patients into low and high CC-CCD groups (< 160 vs. ≥ 160 mg/m2). There was significant improvement in 5-year DFS (91.2% vs. 72.6%; P = 0.003) for patients receiving high CC-CCD compared to those receiving low CC-CCD. Multivariate analysis revealed that CC-CCD, T stage, and Epstein–Barr virus (EBV) DNA were independent prognostic factors for DFS (P < 0.05 for all). Patients were further categorized into two prognostic groups by RPA: the low-risk group (T1-3 disease with regardless of EBV DNA, and T4 disease with EBV DNA < 4000 copy/mL), and the high-risk group (T4 disease with EBV DNA ≥ 4000 copy/mL). Significant 5-year DFS improvement was observed for the high-risk group (P = 0.004) with high CC-CCD. However, DFS improvement was relatively insignificant in the low-risk group (P = 0.073).

Conclusions

CC-CCD was a positive prognostic factor for responders after NAC in CA-LANPC. Furthermore, CC-CCD ≥ 160 mg/m2 could significantly improve DFS in the high-risk group with CA-LANPC, but the benefit of high CC-CCD in the low-risk group needs further study.