bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic tools for return-to-play decisions in sports-related concussion
Authors: Wellm Dennis , Zentgraf Karen
Published: July 2023

Research has improved the understanding of sports related concussion (SRC), and several classification systems and guidelines are available in the literature. The exact timing and clearing of athletes for return-to-play (RTP) is still based primarily on subjective reports of concussion symptoms, however symptoms link poorly to objective recovery. Current literature suggest that symptoms alone cannot accurately identify either all concussed athletes or their recovery. The difficult task of interpreting which symptoms are directly related to concussion, and which are related to other conditions, speaks for an increased focus on the RTP process itself. This study examines the literature on neurocognitive assessments and their importance as indicators of accurate timing of when athletes can return to either ball training with duels or the playing field. Entries in three electronic databases (PubMed, Web of Science, and SURF) were searched from January 2000 to June 2022. Search terms were concussion, mild traumatic brain injury (mTBI), sport, athlete, expert, elite, professional, diagnostic, testing, return to play, management, neurocognitive, and cognitive. Inclusion criteria comprised performance-based participation in a team sport and being in the age range of possible peak performance (18–40 years). In addition, only studies with pre-post designs were considered. The PEDro scale was used to assess methodological quality. The methodological quality of the fifteen included studies ranged from 5 (one study) to 6 (fourteen studies) from a maximum of 10. Despite being symptom-free, athletes in all fifteen studies showed lower performance compared to controls on tests of visual and verbal memory (approx. 3–5% deficit) and on processing speed (approx. 6% deficit) after mTBI. All studies report specific neurocognitive deficits after mTBI, although the athletes were declared clinically symptom-free. Therefore, the systematic consideration of neurocognitive parameters in RTP decision making is recommended, especially in light of subsequent muscular injuries of the lower musculoskeletal system, recurrence of mTBI, and residual neurodegenerative disorders.
Samples from patients with AML show high concordance in detection of mutations by NGS at local institutions vs central laboratories
Authors: Borate Uma , Yang Fei , Press Richard , Ruppert Amy S. , Jones Dan , Caruthers Sean , Zhao Weiqiang , Vergilio Jo-Anne , Pavlick Dean C. , Juckett Luke , Norris Brianna , Bucy Taylor , Burd Amy , Stein Eytan M. , Patel Prapti , Baer Maria R. , Stock Wendy , Schiller Gary , Blum William , Kovacsovics Tibor , Litzow Mark , Foran James , Heerema Nyla A. , Rosenberg Leonard , Marcus Sonja , Yocum Ashley , Stefanos Mona , Druker Brian , Byrd John C. , Levine Ross L. , Mims Alice
Published: July 2023

Next-generation sequencing (NGS) to identify pathogenic mutations is an integral part of acute myeloid leukemia (AML) therapeutic decision-making. The concordance in identifying pathogenic mutations among different NGS platforms at different diagnostic laboratories has been studied in solid tumors but not in myeloid malignancies to date. To determine this interlaboratory concordance, we collected a total of 194 AML bone marrow or peripheral blood samples from newly diagnosed patients with AML enrolled in the Beat AML Master Trial (BAMT) at 2 academic institutions. We analyzed the diagnostic samples from patients with AML for the detection of pathogenic myeloid mutations in 8 genes (DNMT3A, FLT3, IDH1, IDH2, NPM1, TET2, TP53, and WT1) locally using the Hematologic Neoplasm Mutation Panel (50-gene myeloid indication filter) (site 1) or the GeneTrails Comprehensive Heme Panel (site 2) at the 2 institutions and compared them with the central results from the diagnostic laboratory for the BAMT, Foundation Medicine, Inc. The overall percent agreement was over 95% each in all 8 genes, with almost perfect agreement (κ > 0.906) in all but WT1, which had substantial agreement (κ = 0.848) when controlling for site. The minimal discrepancies were due to reporting variants of unknown significance (VUS) for the WT1 and TP53 genes. These results indicate that the various NGS methods used to analyze samples from patients with AML enrolled in the BAMT show high concordance, a reassuring finding given the wide use of NGS for therapeutic decision-making in AML.
Treatment with GLP-1 receptor agonists is associated with significant weight loss and favorable headache outcomes in idiopathic intracranial hypertension
Authors: Krajnc Nik , Itariu Bianca , Macher Stefan , Marik Wolfgang , Harreiter Jürgen , Michl Martin , Novak Klaus , Wöber Christian , Pemp Berthold , Bsteh Gabriel
Published: July 2023

Background

In idiopathic intracranial hypertension (IIH), sustained weight loss is the main pillar in modifying disease course, whereby glucagon-like peptide-1 receptor agonists (GLP-1-RAs) could present an attractive treatment option.

Methods

In this open-label, single-center, case–control pilot study, patients with IIH (pwIIH) and a body mass index (BMI) of ≥ 30 kg/m2 were offered to receive a GLP-1-RA (semaglutide, liraglutide) in addition to the usual care weight management (UCWM). Patients electing for UCWM only served as a control group matched for age-, sex- and BMI (1:2 ratio). The primary endpoint was the percentage weight loss at six months (M6) compared to baseline. Secondary endpoints included the rate of patients with a weight loss of ≥ 10%, monthly headache days (MHD), the rate of patients with a ≥ 30% and ≥ 50% reduction in MHD, visual outcome parameters, and adverse events (AEs).

Results

We included 39 pwIIH (mean age 33.6 years [SD 8.0], 92.3% female, median BMI 36.3 kg/m2 [IQR 31.4–38.3]), with 13 patients being treated with GLP-1-RAs. At M6, mean weight loss was significantly higher in the GLP-1-RA group (–12.0% [3.3] vs. –2.8% [4.7]; p < 0.001). Accordingly, weight loss of ≥ 10% was more common in this group (69.2% vs. 4.0%; p < 0.001). Median reduction in MHD was significantly higher in the GLP-1-RA group (–4 [–10.5, 0.5] vs. 0 [–3, 1]; p = 0.02), and the 50% responder rate was 76.9% vs. 40.0% (p = 0.04). Visual outcome parameters did not change significantly from baseline to M6. Median reduction in acetazolamide dosage was significantly higher in the GLP-1-RA group (–16.5% [–50, 0] vs. 0% [–25, 50]; p = 0.04). AEs were mild or moderate and attributed to gastrointestinal symptoms in 9/13 patients. None of the AEs led to premature treatment discontinuation.

Conclusions

This open-label, single-center pilot study suggests that GLP-1-RAs are an effective and safe treatment option for achieving significant weight loss with a favorable effect on headache, leading to reduced acetazolamide dosage in pwIIH.

Graphical Abstract
Panax notoginseng transcription factor WRKY15 modulates resistance to Fusarium solani by up-regulating osmotin-like protein expression and inducing JA/SA signaling pathways
Authors: Su Linlin , Zheng Lilei , Wang Hanlin , Qu Yuan , Ge Feng , Liu Diqiu
Published: July 2023

Background

Panax notoginseng (Burk) F. H. Chen is a valuable traditional Chinese medicinal plant, but its commercial production is seriously affected by root rot caused by some pathogenic fungi, including Fusarium solani. Nevertheless, the genetic breeding for disease resistance of P. notoginseng remains limited. The WRKY transcription factors have been revealed to play important roles in plant defense responses, which might provide an inspiration for resistance improvement in P. notoginseng.

Results

In this study, the regulatory mechanism of transcription factor PnWRKY15 on P. notoginseng resistance to F. solani infection was revealed. The suppressed expression of PnWRKY15 via RNA interference increased the sensitivity of P. notoginseng to F. solani and decreased the expression levels of some defense-related genes, including PnOLP1, which encodes an osmotin-like protein that confers resistance to F. solani. Ectopic expression of PnWRKY15 in the model plant tobacco significantly enhanced the resistance to F. solani. Moreover, the transcriptome sequencing analysis discovered that some pathogenesis-related genes were expressed at higher levels in the PnWRKY15-overexpressing tobacco than that in the wild-type tobacco. In addition, the jasmonic acid (JA) and salicylic acid (SA) signaling pathways were evidently induced by PnWRKY15-overexpression, that was evidenced by that the JA and SA contents were significantly higher in the PnWRKY15-overexpressing tobacco than that in the wild-type. Furthermore, PnWRKY15, which was localized in the nucleus, can trans-activate and up-regulate PnOLP1 expression according to the EMSA, yeast one-hybrid and co-expression assays.

Conclusions

PnWRKY15 contributes to P. notoginseng resistance to F. solani by up-regulating the expression of resistance-related gene PnOLP1 and activating JA/SA signaling pathways. These findings will help to further elucidate the transcriptional regulatory mechanism associated with the P. notoginseng defense response to F. solani.
The QUILT study: quilting sutures in patients undergoing breast cancer surgery: a stepped wedge cluster randomized trial study
Authors: Zeelst L. J. van , ten Wolde B. , Plate J. D. J. , Volders J. H. , van Eekeren R.R.J.P. , Doeksen A. , Hoven-Gondrie M. L. , Olieman A. F. T. , van Riet Y. E. A. , van der Velden A. P. Schouten , Vijfhuize S. , Witjes H. H. G. , de Wilt J. H. W. , Strobbe L. J. A.
Published: July 2023

Background

Seroma is the most common complication following breast cancer surgery, with reported incidence up to 90%. Seroma causes patient discomfort, is associated with surgical site infections (SSI), often requires treatment and increases healthcare consumption. The quilting suture technique, in which the skin flaps are sutured to the pectoralis muscle, leads to a significant reduction of seroma with a decrease in the number of aspirations and surgical site infections. However, implementation is lagging due to unknown side effects, increase in operation time and cost effectiveness. Main objective of this study is to assess the impact of large scale implementation of the quilting suture technique in patients undergoing mastectomy and/or axillary lymph node dissection (ALND).

Methods

The QUILT study is a stepped wedge design study performed among nine teaching hospitals in the Netherlands. The study consists of nine steps, with each step one hospital will implement the quilting suture technique. Allocation of the order of implementation will be randomization-based. Primary outcome is ‘textbook outcome’, i.e.no wound complications, no re-admission, re-operation or unscheduled visit to the outpatient clinic and no increased use of postoperative analgesics. A total of 113 patients is required based on a sample size calculation. Secondary outcomes are shoulder function, cosmetic outcome, satisfaction with thoracic wall and health care consumption. Follow-up lasts for 6 months.

Discussion

This will be one of the first multicentre prospective studies in which quilting without postoperative wound drain is compared with conventional wound closure. We hypothesize that quilting is a simple technique to increase textbook outcome, enhance patient comfort and reduce health care consumption.
Semi-automated quantification of vitreal hyperreflective foci in SD-OCT and their relevance in patients with peripheral retinal breaks
Authors: Strzalkowski P. , Schuster A. K. , Strzalkowska A. , Steinberg J. S. , Dithmar S.
Published: July 2023

Background

Retinal breaks (RB) are emergencies that require treatment to prevent progression of rhegmatogenous retinal detachment. Vitreal hyperreflective foci (VHF) representing migration of RPE cell clusters or interphotoreceptor matrix from the RB are potential biomarkers. The aim of this study is to investigate VHF in RB-patients using SD-OCT.

Methods

The retrospective cross-sectional study included RB patients from our Department of Ophthalmology, HSK Wiesbaden who underwent macular SD-OCT (SPECTRALIS®, Heidelberg Engineering, Germany) on both eyes. VHF, defined and quantified as foci that differ markedly in size and reflectivity from the background speckle pattern, were assessed for presence and frequency. The RB-affected eyes were the study group (G1), the partner eyes the control group (G2).

Results

160 consecutive patients with RB were included. Age was 60 ± 10.2 years (52% female). 89.4% of G1 and 87.5% of G2 were phakic (p = 0.73). 94.4% (n = 151) were symptomatic. Symptom duration was 8.0 ± 10.1 days in G1, 94.4% (n = 151) showed VHF versus 5.6% (p < 0.0001) in G2, of which 75% (n = 6) showed asymptomatic lattice degenerations. Detectable VHF showed a strong association of OR = 320 (95% CI, 110–788, p < 0.0001)) with respect to symptomatic RB. Sensitivity and specificity were 94.7% and 94.7%, respectively.

Conclusions

Most eyes with symptomatic RB show vitreal VHF in SD-OCT. Detected VHF are strongly associated with RB, and our semi-automated greyscale reflectivity analysis indicates that VHF likely originate from photoreceptor complexes torn out of the RB area that migrate into the vitreous cavity. The presence of VHF may indicate RB and should lead to a thorough fundus examination in both symptomatic and asymptomatic cases.
Knowledge, perceptions and uptake of human papilloma virus vaccine among adolescent girls in Kampala, Uganda; a mixed-methods school-based study
Authors: Bitariho Glet Kakuru , Tuhebwe Doreen , Tigaiza Arnold , Nalugya Aisha , Ssekamatte Tonny , Kiwanuka Suzanne N
Published: July 2023

Background

Cervical cancer is a major public health challenge, accounting for substantial morbidity and mortality. Human Papilloma Virus (HPV) vaccination is the recommended primary public health intervention for HPV infection prevention. However, there’s limited evidence on the level of knowledge, attitude, and practices of adolescent girls regarding HPV vaccination in Kampala city, Uganda. This study assessed the knowledge, perceptions, and practices of adolescent girls aged 10-14 years towards HPV vaccination program in Kampala, Uganda to generate evidence to guide programs targeted at improving uptake of the vaccine.

Methods

A convergent parallel mixed methods study was conducted in Kampala, Uganda. A structured questionnaire was used to elicit data from 524 adolescent girls. In addition, 6 Focus group discussions, and 24 key informant interviews (teacher and parents) were conducted. Multistage and purposive sampling techniques were used to select quantitative and qualitative participants respectively. Quantitative data were entered using epidata, cleaned and analyzed using Stata v14 while qualitative data were analyzed using thematic content analysis in atlas ti version 8.

Results

Overall, only 8.6% (45/524) of the girls had completed the HPV vaccine schedule of two dozes, 49.2% (258/524) of the girls had low knowledge about the HPV vaccine and teachers and parents affirmed this lack of knowledge among adolescent girls especially concerning the target age group, dosage, and vaccine interval. About 51.9% (272/524) of girls had negative perceptions towards HPV vaccination. Parents expressed negative perceptions, beliefs, superstitions, and safety concerns of the vaccine.Girls residing in rural areas (adjusted prevalence ratio, aPR = 0.35, C. I = 0.14–0.85) had lower knowledge levels compared to those in urban areas. Girls whose mothers were healthcare providers (aPR = 1.94, C. I = 1.10–3.41), girls with high knowledge levels (aPR = 1.79, C. I = 1.21–2.63) and positive perceptions (aPR = 2.87, C. I = 1.93–4.27) had a higher prevalence of being fully vaccinated.

Conclusion

Girls generally had low levels of knowledge, negative perceptions, and poor uptake of HPV vaccination. We recommend sensitization campaigns in schools and communities to improve awareness, perceptions, and practices of stakeholders towards HPV vaccination.
Using the Behaviour Change Wheel and modified Delphi method to identify behavioural change techniques for improving adherence to smoking cessation medications
Authors: Mersha Amanual Getnet , Kennedy Michelle , Eftekhari Parivash , Lee KS Kylie , Upton Penney , Segan Catherine , Jackson Melissa A. , Jennings Kirsty , Gould Gillian Sandra
Published: July 2023

Background

Medication adherence is a crucial component of the pharmacological treatment of smoking. Previous interventions targeted to improve adherence to smoking cessation medications (SCMs) were designed using pragmatic approaches. This study aims to develop a comprehensive intervention strategy to improve adherence to SCMs using the Behaviour Change Wheel (BCW) and a modified Delphi method.

Methods

Recommendations for the design of intervention strategies were based on the BCW guide and six studies conducted by the research team. Factors related to healthcare providers and consumers (person making a quit attempt) that showed associations with adherence were mapped into the Capability, Opportunity, Motivation, Behaviour (COM-B) model, and corresponding intervention functions and policy categories. Interventions were then represented using the Behaviour Change Technique Taxonomy. Finally, a modified Delphi study using 17 experts was conducted to evaluate the nominated strategies using the Acceptability, Practicability, Effectiveness, Affordability, Side-effects, and Equity (APEASE) criteria.

Results

Following a stepped approach, an adherence support wheel was designed to guide implementation strategies and programmes. Thirteen intervention strategies were selected. The selected interventions include providing detailed instructions on how to use SCMs; establishing realistic expectations from SCMs; and providing training for healthcare providers regarding comprehensive smoking cessation care with specifics on the provision of adherence support.

Conclusion

The BCW guide and a modified Delphi were applied successfully to design interventions tailored to improve adherence to SCMs. Improving adherence to SCMs requires a comprehensive intervention approach involving various stakeholders. Future research is needed to assess the effectiveness of the nominated intervention strategies.
Association between breastfeeding and periodontitis in Korean women using Korea National Health and Nutrition Examination Survey (KNHANES): a cross-sectional study
Authors: Wang Zi-Lan , Ryu Seung-Hee , Bae Kwang-Hak , Kim Seon-Jip , Cho Hyun-Jae
Published: July 2023

Objectives

The effect of breastfeeding on periodontal disease in women remains unclear. This cross-sectional study used data from the Korean National Health and Nutrition Examination Survey to explore the association between breastfeeding and periodontitis in Korean women using data from the Korean National Health and Nutrition Examination Survey (KNHANES VII).

Materials and methods

Cross-sectional data was analyzed from the KNHANES 2016–2018. The study population included 5,587 parous women aged ≥ 30 years. The outcome variable was the presence or absence of periodontitis. The explanatory variable, period of breastfeeding, was defined as “none”, “1–11 months”, and “more than 12 months”. Confounder variables (socio-educational, personal healthcare practice, and systemic medical characteristics) were adjusted for in the logistic regression analysis.

Results

Approximately 60% of the participants breastfed for ≥ 12 months. In all statistical models, the prevalence of periodontitis was approximately 60% greater in women that did not breastfeed compared to women that had breastfed for 12 months or longer. When adjusted for age, statistical significance was only present in the 50–59 years age group (adjusted odds ratio [aOR], 1.678; 95% confidence interval [CIs], 1.046–2.691).

Conclusion

Our study shows that women that breastfed for a relatively long duration had a lower risk of periodontitis. Therefore, breastfeeding may be beneficial for women’s periodontal health. These results are expected to be helpful in oral health education for pregnant women.
Translation and psychometric validation of the Persian version of palliative care attitudes scale in cancer patients
Authors: Bagheri Sajjad , Barkhordari-Sharifabad Maasoumeh
Published: July 2023

Introduction

To improve cancer patients’ quality of life, palliative care is necessary. The growth of palliative care, along with the assistance of the government and the collaboration of specialists, also relies on the knowledge and attitude of people. In Iran, there is no tool available to gauge patient attitudes about palliative treatment. The Persian version of the Palliative Care Attitude Scale (PCAS-9) was translated and psychometrically validated in this research among cancer patients.

Methods

This methodological study was conducted in two stages: translation stage and psychometric validation stage. The method of translation was based on that proposed by Polit and Yang. Utilizing a qualitative approach, the scale’s face and content validity were investigated. 162 cancer patients who required palliative care based on expert diagnosis participated in the confirmatory factor analysis to establish construct validity. Stability and internal consistency provided evidence of reliability. The data was examined using SPSS18 and AMOS.

Results

The “Palliative Care Attitudes Scale” translated well across cultures. Validity on both the face and the content was acceptable. Confirmatory factor analysis (CFA) revealed a good fit for the original three-factor structure. The intra-class correlation coefficient (ICC) was equal to 0.89, while the internal consistency (Cronbach’s alpha) reliability of the whole scale was equal to 0.77.

Conclusions

Persian version of the “Palliative Care Attitudes Scale” was acceptable and adequate in cancer patients. Using this tool makes it easier to assess how patients feel about receiving palliative care and how well training sessions are working to change patients’ views.
Shenkang protects renal function in diabetic rats by preserving nephrin expression
Authors: Qu Zhihui , Wang Biyao , Jin Yingli , Xiao Qingfei , Zhao Ying , Zhao Danning , Yang Liming
Published: July 2023

Background

Shenkang injection has been used clinically to lower creatinine levels. This study explored the mechanism of Shenkang injection on protecting kidney function from hyperglycemia-mediated damage.

Methods

This study utilized a STreptoZotocin (STZ)-induced rat model of diabetes. In total, 60 rats were randomized into either the control group (n = 15) injected with vehicle or treatment group (n = 45) injected with STZ to induce hyperglycemia. Eight weeks after diabetes onset, diabetic rats were further randomized to receive different treatments for 4 consecutive weeks, including vehicle (diabetic nephropathy group, n = 15), Shenkang (n = 15), or Valsartan (n = 15). At 12 weeks, a series of urine and blood measures were examined and damage to the kidney tissue was examined using histology. Expression of nephrin and transforming growth factor-β1 (TGF-β1) were characterized using immunohistochemistry and Western blot.

Results

Compared to the control group, rats in the diabetic nephropathy group showed significant kidney damage demonstrated by high kidneyindex, high levels of urinary albumin, albumin/creatinine ratio (ACR), blood urea nitrogen as well as histological evidence. Shenkang injection significantly improved kidney function in the diabetic rats by decreasing kidney index, ACR, and serum creatinine. Shenkang treatment also mitigated kidney damage, improved nephrin expression, and decreased TGF-β1 expression in the kidneys.

Conclusions

Shenkang treatment protected renal function in diabetic rats by increasing nephrin expression, which protects diabetic rats from hyperglycemia-mediated kidney damage.
The linkage of NF-κB signaling pathway-associated long non-coding RNAs with tumor microenvironment and prognosis in cervical cancer
Authors: Feng Xue , Shan Ru , Hu Xiaomeng
Published: July 2023

Background

NF-κB signaling pathway participate closely in regulating inflammation and immune response in many cancers. Long non-coding RNAs (lncRNAs) associated with NF-κB signaling have not been characterized in cervical cancer. This study revealed the linkage between tumor microenvironment and NF-κB signaling-associated lncRNAs in cervical cancer.

Materials and methods

The expression profiles of cervical cancer samples from The Cancer Genome Atlas (TCGA) database were downloaded. NF-κB signaling-associated lncRNAs were screened as a basis to perform molecular subtyping. Immune cell infiltration was assessed by ESTIMATE, Microenvironment Cell Populations (MCP)-counter and single sample gene set enrichment analysis (ssGSEA). The key NF-κB signaling-associated lncRNAs were identified by univariate analysis, least absolute shrinkage and selection operator, and stepAIC.

Results

Three molecular subtypes or clusters (cluster 3, cluster 2, and cluster 1) were categorized based on 27 prognostic NF-κB signaling-associated lncRNAs. Cluster 2 had the worst prognosis, highest immune infiltration, as well as the highest expression of most of immune checkpoints. Three clusters showed different sensitivities to immunotherapy and chemotherapy. Six key NF-κB signaling-associated lncRNAs were screened to establish a six-lncRNA risk model for predicting cervical cancer prognosis.

Conclusions

NF-κB signaling-associated lncRNAs played an important role in regulating immune microenvironment. The subtyping based on NF-κB signaling-associated lncRNAs may assist in the selection of optimal treatments. The six key NF-κB signaling-associated lncRNAs could act as prognostic biomarkers in prognostic prediction for cervical cancer.
Seeking maternal health care in rural Nigeria: through the lens of negofeminism
Authors: Udenigwe Ogochukwu , Okonofua Friday E. , Ntoimo Lorretta F. C. , Yaya Sanni
Published: July 2023

Background

Feminist scholarship is acutely aware that health is not dependent on behavioural choices alone but on interlocking social determinants that affect people’s capacity to lead healthy lives. Women are situated within social structures that impact their health. but there is limited engagement with interpretive tools such as feminist theories that centre the realities of African women, particularly in the context of maternal health. It is imperative that women’s control over their reproductive health and autonomy in seeking care, particularly skilled maternal healthcare are understood within this context. This study seeks to examine pregnant women’s socio-cultural realities in a Nigerian context and in congruence with articulations of African feminism. Feminist scholarship acknowledges that women are situated within social structures that impact their health. Therefore, this paper seeks to examine pregnant women’s socio-cultural realities in a Nigerian context and in congruence with articulations of African feminism.

Method

This is a cross-sectional qualitative study of a total of 64 participants: 39 women and 25 men in Ewato and Okpekpe communities, two Local Government Areas of Edo State in southern Nigeria. The study presents findings from eight sex-and-age desegregated focus group discussions. This study reports on emergent data related to women’s decision-making in accessing skilled maternal care. Data were transcribed and translated to English. Using the NVivo 1.6 software, data were coded and analyzed using a conventional approach to content analysis.

Results

Findings describe ways in which women negotiate authority by ascribing the role of decision-maker to their men spouses while maintaining influence over their pregnancy healthcare decisions and actions. Negofeminism’s concepts of alliance, community and connectedness were highlighted through men’s constructive involvement in maternal health. Furthermore, women were shown to maneuver patriarchal norms to gain control of their healthcare decisions.

Conclusion

This study offers a different narrative from the dominant view of non-Western women, specifically African women, as oppressed passive victims who are ineffectual in taking charge of their health. From the perspective of negofeminism, women navigate patriarchal environments to yield the best possible maternal health outcomes. The current study can be useful in informing policy and programming that acknowledges women’s social embeddedness.
Use of electronic patient records and encrypted email patient communication among Swiss chiropractors: a population-based cross-sectional study
Authors: Hincapié Cesar A. , Hofstetter Léonie , Lalji Rahim , Korner Longin , Schläppi Mireille C. , Leemann Serafin
Published: July 2023

Background

The implementation of electronic health information technologies is a key target for healthcare quality improvement. Among Swiss chiropractors, reliable data on the use of electronic heath information technologies and distribution of the health workforce was lacking.

Objectives

To estimate the prevalence of electronic patient record (EPR) and encrypted email communication use among Swiss chiropractors and describe the geographic distribution of chiropractors in Switzerland.

Methods

Population-based cross-sectional study of all active practising members of the Swiss Chiropractic Association (ChiroSuisse) between 3 December 2019 and 31 January 2020. We asked about clinician and practice characteristics, EPR use for clinical record keeping, use of encrypted email for patient communication, and information on EPR and encrypted email communication products used. Multivariable logistic regression analyses assessed the associations between clinician and practice characteristics and (1) EPR use, and (2) encrypted email use.

Results

Among 286 eligible Swiss chiropractors (193 [68%] men; mean age, 51.4 [SD, 11.2] years), 217 (76%) completed the survey (140 [65%] men; mean age 50.7 [11.2] years). Among respondents, 47% (95% confidence interval [CI], 40–54%) reported using an EPR in their practice, while 60% (95% CI, 54–67%) endorsed using encrypted email technology. Chiropractors aged ≥ 60 (versus those ≤ 39) years were 74% less likely to use an EPR system (OR 0.26, 95% CI 0.08 to 0.77), while clinicians from practices with 4 or more chiropractors (versus those from solo practices) were over 5 times more likely to report EPR use (OR 5.6, 2.1 to 16.5). Findings for factors associated with encrypted email use were similar. The density of chiropractors in Switzerland was 3.3 per 100,000 inhabitants.

Conclusions

As of January 2020, 286 duly licensed chiropractors were available to provide musculoskeletal healthcare in Switzerland — just under 50% of responding Swiss chiropractors used an EPR system in clinical practice, while 60% used encrypted email technology. Better implementation of EPR and electronic health information technologies in Swiss chiropractic practice is possible and encouraged for the purpose of musculoskeletal healthcare quality improvement.
Expandable versus static cages in unilateral biportal endoscopy lumbar interbody fusion (ULIF) for treating degenerative lumbar spondylolisthesis (DLS): comparison of clinical and radiological results
Authors: Cao Shuyan , Fan Bingjie , Song Xin , Wang Yi , Yin Wenzhe
Published: July 2023

Background

In recent years, early rehabilitation after spinal fusion and the recovery of physiological curvature have attracted much attention. Therefore, expandable cages have entered the field of vision of scientists. The goal of the current study was to compare the clinical and radiological results of unilateral portal endoscopic lumbar interbody fusion (ULIF) in the treatment of degenerative lumbar spondylolisthesis (DLS) with expandable versus static cages.

Methods

We retrospectively analysed patients who received ULIF treatment for DLS from May 2019 to February 2021. Patients were categorized by cage type (static vs. expandable), and the main study was the preop and postop clinical and radiological index changes of the patients.

Results

Eighty-four patients were included (38 in the static cages group; 46 in the expandable cages group). There was no difference in the preop results between the two groups. The VAS scores for low back and leg pain and ODI scores in the expandable cages group 7 d postop were significantly superior to those in the static cages group (P < 0.05), and the segmental angle and PDH in the expandable cages group postop were significantly higher than those in the static cages group (P < 0.05). The fusions at 6 m postop in the expandable cages group were superior to those in the Static Cages group (P < 0.05).

Conclusions

The results of this study showed that compared with the stable cage group, the expandable cage group had unique advantages in restoring the physiological curvature of the lumbar spine, increasing the fusion rate, and relieving pain in the early postoperative period. ULIF can be used to treat single-segment, mild lumbar spondylolisthesis patients using expandable cages instead of static cages.
Characterization of the stanford integrated psychosocial assessment for transplant for heart, liver, and kidney transplant candidates in Japan
Authors: Takano Kosuke , Oshibuchi Hidehiro , Kobayashi Sayaka , Tsutsui Junko , Ito Satoko , Kamba Rumiko , Akaho Rie , Nishimura Katsuji
Published: July 2023

Background

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a comprehensive psychosocial assessment proven useful for predicting the outcomes of organ transplantation that is expected to be useful in Japan. However, the characteristics of organ-specific SIPAT scores for organ transplant recipient candidates in Japan are unclear and, to date, the SIPAT has not been properly utilized in clinical practice. The purpose of this study was to present basic data that can be used to establish the relation between SIPAT scores and post-transplantation psychosocial outcomes as well as organ-specific outcomes.

Methods

This study included 167 transplant recipient candidates (25 heart, 71 liver, and 71 kidney) who completed a semi-structured interview based on the Japanese version of SIPAT (SIPAT-J) prior to transplantation. The differences between organs in terms of SIPAT scores and differences in SIPAT scores based on demographic data were comparatively analyzed.

Results

The total SIPAT scores were higher for liver recipient candidates than for heart recipient candidates (P = .019). Regarding the subscales, SIPAT B (social support system) scores were higher for liver and kidney recipient candidates than for heart recipient candidates (P = .021), whereas SIPAT C (psychological stability and psychopathology) scores were higher for liver recipient candidates than for kidney recipient candidates (P = .002). Recipient candidates with a history of psychiatric treatment and those who were unemployed had higher SIPAT scores, regardless of the transplant organ, than recipient candidates without a history of psychiatric treatment and those who were employed (P < .001, P = .016, respectively).

Conclusions

There were notable differences in the total SIPAT-J and subscale scores among the liver, heart, and kidney recipient candidates. Each organ was associated with specific psychosocial issues that should be addressed before transplantation. Interventions such as information provision and patient education based on SIPAT assessment results for each organ may improve recipient post-transplant outcomes.
Study of the regulatory elements of the Ovalbumin gene promoter using CRISPR technology in chicken cells
Authors: Yousefi Taemeh Sara , Dehdilani Nima , Goshayeshi Lena , Rival-Gervier Sylvie , Mehrzad Jalil , Pain Bertrand , Dehghani Hesam
Published: July 2023

Background

Hormone-dependent promoters are very efficient in transgene expression. Plasmid-based reporter assays have identified regulatory sequences of the Ovalbumin promoter that are involved in response to estrogen and have shown that the deletion of the steroid-dependent regulatory element (SDRE) and negative regulatory element (NRE) leads to a steroid-independent expression of a reporter. However, the functional roles of these regulatory elements within the native genomic context of the Ovalbumin promoter have not been evaluated.

Results

In this study, we show that the negative effects of the NRE element on the Ovalbumin gene can be counteracted by CRISPR interference. We also show that the CRISPR-mediated deletion of SDRE and NRE promoter elements in a non-oviduct cell can lead to the significant expression of the Ovalbumin gene. In addition, the targeted knock-in of a transgene reporter in the Ovalbumin coding region and its expression confirms that the truncated promoter of the Ovalbumin gene can be efficiently used for an estrogen-independent expression of a foreign gene.

Conclusions

The methodology applied in this paper allowed the study of promoter regulatory sequences in their native nuclear organization.
The clinical significance of low dose biotin supplements (<300μg/day) in the treatment of patients with hypothyroidism: crucial or overestimated?
Authors: Angelopoulos Nicholas , Paparodis Rodis D. , Androulakis Ioannis , Anagnostis Panagiotis , Boniakos Anastasios , Duntas Leonidas , Karras Spyridon N. , Livadas Sarantis
Published: July 2023

Background

In the last decade, the combination of the widespread use of streptavidin–biotin technology and biotin–containing supplements (BCS) in the daily clinical practice, have led to numerous reports of erroneous hormone immunoassay results. However, there are no studies assessing the clinical and biochemical significance of that phenomenon, when treating patients with hypothyroidism. Therefore, a prospective study was designed to investigate the potential alterations in the measurement of thyroid hormone concentrations and clinical consequences in patients with hypothyroidism using low -dose BCS containing less than 300 μg/day.

Methods

Fifty-seven patients on thyroxine supplementation, as a result of hypothyroidism and concurrent use of BCS at a dose <300μg/day for 10 to 60 days were prospectively evaluated. Namely, TSH and free T4 (FT4) concentration measurements were performed, during BC supplementation and 10 days post BCS discontinuation and compared to 31 age-matched patients with supplemented hypothyroidism and without BCS.

Results

A statistically significant increase in TSH and decline in FT4 concentrations was observed after BCS discontinuation. However, on clinical grounds, these modifications were minor and led to medication dose adjustment in only 2/57 patients (3.51%) in whom TSH was notably decreased after supplement discontinuation.

Conclusion

Our study suggests that changes in thyroid hormones profiling, due to supplements containing low dose biotin, are of minimal clinical relevance and in most cases don’t occult the need to adjust the thyroxine replacement dose in patients with hypothyroidism. Larger, well-designed trials are required to further evaluate this phenomenon.
Interrogating colorectal cancer metastasis to liver: a search for clinically viable compounds and mechanistic insights in colorectal cancer Patient Derived Organoids
Authors: Cioce Mario , Fumagalli Maria Rita , Donzelli Sara , Goeman Frauke , Canu Valeria , Rutigliano Daniela , Orlandi Giulia , Sacconi Andrea , Pulito Claudio , Palcau Alina Catalina , Fanciulli Maurizio , Morrone Aldo , Diodoro Maria Grazia , Caricato Marco , Crescenzi Anna , Verri Martina , Fazio Vito Michele , Zapperi Stefano , Levrero Massimo , Strano Sabrina , Grazi Gian Luca , La Porta Caterina , Blandino Giovanni
Published: July 2023

Background

Approximately 20–50% of patients presenting with localized colorectal cancer progress to stage IV metastatic disease (mCRC) following initial treatment and this is a major prognostic determinant. Here, we have interrogated a heterogeneous set of primary colorectal cancer (CRC), liver CRC metastases and adjacent liver tissue to identify molecular determinants of the colon to liver spreading. Screening Food and Drug Administration (FDA) approved drugs for their ability to interfere with an identified colon to liver metastasis signature may help filling an unmet therapeutic need.

Methods

RNA sequencing of primary colorectal cancer specimens vs adjacent liver tissue vs synchronous and asynchronous liver metastases. Pathways enrichment analyses. The Library of Integrated Network-based Cellular Signatures (LINCS)-based and Connectivity Map (CMAP)-mediated identification of FDA-approved compounds capable to interfere with a 22 gene signature from primary CRC and liver metastases. Testing the identified compounds on CRC-Patient Derived Organoid (PDO) cultures. Microscopy and Fluorescence Activated Cell Sorting (FACS) based analysis of the treated PDOs.

Results

We have found that liver metastases acquire features of the adjacent liver tissue while partially losing those of the primary tumors they derived from. We have identified a 22-gene signature differentially expressed among primary tumors and metastases and validated in public databases. A pharmacogenomic screening for FDA-approved compounds capable of interfering with this signature has been performed. We have validated some of the identified representative compounds in CRC-Patient Derived Organoid cultures (PDOs) and found that pentoxyfilline and, to a minor extent, dexketoprofen and desloratadine, can variably interfere with number, size and viability of the CRC –PDOs in a patient-specific way. We explored the pentoxifylline mechanism of action and found that pentoxifylline treatment attenuated the 5-FU elicited increase of ALDHhigh cells by attenuating the IL-6 mediated STAT3 (tyr705) phosphorylation.

Conclusions

Pentoxifylline synergizes with 5-Fluorouracil (5-FU) in attenuating organoid formation. It does so by interfering with an IL-6-STAT3 axis leading to the emergence of chemoresistant ALDHhigh cell subpopulations in 5-FU treated PDOs. A larger cohort of CRC-PDOs will be required to validate and expand on the findings of this proof-of-concept study.
Using a multistep approach with multidisciplinary team to increase the diagnosis rate of Lynch syndrome-associated colorectal cancer after universal screening: a single-center study in Japan
Authors: Tatsuta Kyota , Sakata Mayu , Iwaizumi Moriya , Kojima Risa , Yamanaka Katsumasa , Baba Satoshi , Suzuki Katsunori , Morita Yoshifumi , Kikuchi Hirotoshi , Hiramatsu Yoshihiro , Kurachi Kiyotaka , Takeuchi Hiroya
Published: July 2023

Backgrounds

: This study aimed to evaluate the changes in the rates of genetic counseling and genetic testing as well as the diagnosis rate of Lynch syndrome (LS)-associated colorectal cancer before and after multistep approach with multidisciplinary team in Japanese.

Methods

In September 2016, we started universal screening for LS by mismatch repair protein immunohistochemistry and prospectively collected the records. Following patient interviews, we started multistep approach with multidisciplinary team (MA) in January 2020. MA consists of six surgeons, one genetic counselor, one medical geneticist, and six pathologists. MA is set up to compensate for patients’ lack of knowledge about genetic diseases and make case selection for elderly colorectal cancer patients with deficient mismatch repair (dMMR). MA is designed as a system that could be performed by a small number of medical genetic specialists. A total of 522 patients were included during the study duration, 323 and 199 patients in the pre-MA (P-MA) and MA groups, respectively.

Results

The frequency of dMMR in all patients was 10.0%. The patient interview results indicated a significant lack of patient education regarding genetic diseases. The rates of genetic counseling and genetic testing was significantly higher in MA group than in P-MA group (genetic counseling: MA 34.6% vs. P-MA 7.7%, p = 0.04; genetic testing: MA 30.8% vs. P-MA 3.8%, p = 0.02). Moreover, the diagnosis rate of LS-associated colorectal cancer was significantly higher in MA group (2.5%) than in P-MA group (0.3%) (P = 0.03). In addition, MA could be performed without problems despite the small number of medical and human genetics specialists.

Conclusions

MA has achieved appropriate pickup of suspected hereditary colorectal cancer patients and complemented the lack of knowledge about genetic diseases. The introduction of MA increased LS-associated colorectal cancer after universal screening. MA is an appropriate LS screening protocol for Japanese patients who lag behind in medical and human genetics education.
Comprehensive analysis of neoantigens derived from structural variation across whole genomes from 2528 tumors
Authors: Shi Yang , Jing Biyang , Xi Ruibin
Published: July 2023

Background

Neoantigens are critical for anti-tumor immunity and have been long-envisioned as promising therapeutic targets. However, current neoantigen analyses mostly focus on single nucleotide variations (SNVs) and indel mutations and seldom consider structural variations (SVs) that are also prevalent in cancer.

Results

Here, we develop a computational method termed NeoSV, which incorporates SV annotation, protein fragmentation, and MHC binding prediction together, to predict SV-derived neoantigens. Analysis of 2528 whole genomes reveals that SVs significantly contribute to the neoantigen repertoire in both quantity and quality. Whereas most neoantigens are patient-specific, shared neoantigens are identified with high occurrence rates in breast, ovarian, and gastrointestinal cancers. We observe extensive immunoediting on SV-derived neoantigens, especially on clonal events, which suggests their immunogenic potential. We also demonstrate that genomic alteration-related neoantigen burden, which integrates SV-derived neoantigens, depicts the tumor-immune interplay better than tumor neoantigen burden and may improve patient selection for immunotherapy.

Conclusions

Our study fills the gap in the current neoantigen repertoire and provides a valuable resource for cancer vaccine development.
Sensitive inference of alignment-safe intervals from biodiverse protein sequence clusters using EMERALD
Authors: Grigorjew Andreas , Gynter Artur , Dias Fernando H. C. , Buchfink Benjamin , Drost Hajk-Georg , Tomescu Alexandru I.
Published: July 2023

﻿Abstract

Sequence alignments are the foundations of life science research, but most innovation so far focuses on optimal alignments, while information derived from suboptimal solutions is ignored. We argue that one optimal alignment per pairwise sequence comparison is a reasonable approximation when dealing with very similar sequences but is insufficient when exploring the biodiversity of the protein universe at tree-of-life scale. To overcome this limitation, we introduce pairwise alignment-safety to uncover the amino acid positions robustly shared across all suboptimal solutions. We implement EMERALD, a software library for alignment-safety inference, and apply it to 400k sequences from the SwissProt database.
MSV: a modular structural variant caller that reveals nested and complex rearrangements by unifying breakends inferred directly from reads
Authors: Schmidt Markus , Kutzner Arne
Published: July 2023

Structural variant (SV) calling belongs to the standard tools of modern bioinformatics for identifying and describing alterations in genomes. Initially, this work presents several complex genomic rearrangements that reveal conceptual ambiguities inherent to the representation via basic SV. We contextualize these ambiguities theoretically as well as practically and propose a graph-based approach for resolving them. For various yeast genomes, we practically compute adjacency matrices of our graph model and demonstrate that they provide highly accurate descriptions of one genome in terms of another. An open-source prototype implementation of our approach is available under the MIT license at https://github.com/ITBE-Lab/MA.