bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of lower-limb mechanical axis on the curative effect of medial high tibial osteotomy for knee osteoarthritis
Authors: Yuan Long , Niu Shuaishuai , Zhai Chuanxing , Li Sen , Bian Jichao , Zhao Xiaowei , Zhang Yuanmin , Wang Guodong
Published: May 2022

Purpose

To investigate the effect of the ratio of the medial tibial plateau width to the total tibial plateau width on the therapeutic efficacy of high tibial osteotomy (HTO) on the medial side for the treatment of knee osteoarthritis.

Methods

In this study, we retrospectively analyzed information of 278 patients who underwent medial HTO for knee osteoarthritis with varus deformity. The Tinetti Gait and Balance Assessment Tool, the Visual Analog Scale (VAS), and the Knee Society Scoring System (KSS) were used to comprehensively evaluate the function of the knee joint after HTO.

Results

After adjusting for potential confounding factors (i.e., age, gender, body mass index/BMI, and surgical site), the Tinetti assessment score was optimized when the degree of correction was 53.67%, with the β-value on the left and right sides of the inflection point of 0.49 (confidence interval, CI: 0.20, 0.78, P = 0.0009) and− 0.26 (95% CI: − 0.30, − 0.22, P < 0.0001), respectively. The KSS score was optimized when the degree of correction was 55.45%, with the β-value on the left and right sides of the inflection point of 2.77 (95% CI: 1.64, 3.90, P < 0.0001) and − 1.18 (95% CI: − 1.46, − 0.91, P < 0.0001), respectively. The VAS score was the lowest when the degree of correction was 55.00%, with the β-value on the left and right sides of the inflection point of − 0.16 (95% CI: − 0.29, − 0.03, P = 0.0146) and 0.08 (95% CI: 0.05, 0.10, P < 0.0001), respectively. Stratified analysis showed that the BMI affected the Tinetti assessment score (β =  − 0.14, 95% CI: − 0.24, − 0.04, P = 0.0071). According to the smooth-curve fitting results, when the BMI was > 28, the Tinetti assessment score showed a negative trend.

Conclusion

The degree of lower-limb mechanical axis correction correlated with the functional status of the knee joint after MOW HTO. When the ratio of the medial tibial plateau width to the total tibial plateau width was approximately 55%, the post-MOW HTO outcomes were optimized and the patients experienced the highest satisfaction. In addition, very high BMI was not conducive for the postoperative recovery of the knee joint function.

Level of evidence: III Case–control study/Retrospective comparative study.
Impact of salvage cytotoxic chemotherapy on prognosis in patients with recurrence after radical cystectomy: a multi-institutional retrospective study
Authors: Koguchi Dai , Matsumoto Kazumasa , Ikeda Masaomi , Taoka Yoshinori , Hirayama Takahiro , Murakami Yasukiyo , Utsunomiya Takuji , Matsuda Daisuke , Okuno Norihiko , Irie Akira , Iwamura Masatsugu
Published: May 2022

Background

In patients experiencing disease recurrence after radical cystectomy (RC) for bladder cancer, data about the impact of clinicopathologic factors, including salvage treatment using cytotoxic chemotherapy, on the survival are scarce. We investigated the prognostic value of clinicopathologic factors and the treatment effect of salvage cytotoxic chemotherapy (SC) in such patients.

Methods

In this retrospective study, we evaluated the clinical data for 86 patients who experienced recurrence after RC. Administration of SC or of best supportive care (BSC) was determined in consultation with the urologist in charge and in accordance with each patient’s performance status, wishes for treatment, and renal function. Statistical analyses explored for prognostic factors and evaluated the treatment effect of SC compared with BSC in terms of cancer-specific survival (CSS).

Results

Multivariate analyses showed that liver metastasis after RC (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.17 to 3.85; P = 0.01) and locally advanced disease at RC (HR 1.92; 95% CI 1.06 to 3.46; P = 0.03) are independent risk factors for worse CSS in patients experiencing recurrence after RC. In a risk stratification model, patients were assigned to one of two groups based on liver metastasis and locally advanced stage. In the high-risk group, which included 68 patients with 1–2 risk factors, CSS was significantly better for patients receiving SC than for those receiving BSC (median survival duration: 9.4 months vs. 2.4 months, P = 0.005). The therapeutic effect of SC was not related to a history of adjuvant chemotherapy.

Conclusions

The present study indicated the potential value of 1st-line SC in patients experiencing recurrence after RC even with advanced features, such as liver metastasis after RC and locally advanced disease at RC.
Association between type 2 diabetes status and prevalence of liver steatosis and fibrosis among adults aged ≥ 40 years
Authors: Chen Jun , Hu Piao , Wang Yanfei , Zhu Zhongxin
Published: May 2022

Background

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease frequently coexist and share pathophysiological manifestations. This study aimed to explore the association between T2DM status and prevalence of liver steatosis and fibrosis, identified using the controlled attenuation parameter and liver stiffness measurement attained via liver ultrasound transient elastography.

Methods

This was a cross-sectional analysis of data collected in the National Health and Nutrition Examination Survey for 2017–2018. Multivariable logistic regression model was used to evaluate the association between T2DM and prevalence of liver steatosis and fibrosis. Subgroup analyses, stratified by sex age, race, and body mass index (BMI), were further performed.

Results

Of the 2,780 participants aged ≥ 40 years enrolled, 749 had T2DM, and 2,031 did not. After adjustment for potential confounders, T2DM was associated with a higher prevalence of liver steatosis (OR = 1.7, 95% CI, 1.3–2.1). This T2DM-related prevalence was higher among women (OR = 1.8, 95% CI, 1.3–2.5) and in the non-Hispanic Black (OR = 1.8, 95% CI, 1.1–3.0), other race (OR = 1.9, 95% CI, 1.2–3.0), and BMI < 25 kg/m2(OR = 2.0, 95% CI, 1.1–3.8) groups. T2DM was also associated with a significantly higher prevalence of fibrosis (OR = 2.0, 95% CI, 1.5–2.7), with this association being more prominent for the other race (OR = 2.9, 95% CI, 1.5–5.5) and BMI < 25 kg/m2(OR = 3.3, 95% CI: 1.3–8.8) groups.

Conclusions

Our findings indicated a positive association between T2DM status and prevalence of hepatic steatosis and fibrosis. This association was more prominent for individuals with a BMI < 25 kg/m2and was influenced by race-specific effects.
Clinical and MRI features of sacral insufficiency fractures after radiotherapy in patients with cervical cancer
Authors: Zhong Xi , Zhang Linqi , Dong Tianfa , Mai Hui , Lu Bingui , Huang Lu , Li Jiansheng
Published: May 2022

Background

To determine the incidence, clinical and MRI features of sacral insufficiency fracture (SIF) after radiotherapy (RT) in patients with cervical cancer.

Methods

Our study included 167 patients with cervical cancer after radiotherapy that underwent pelvic MRI for follow-up. MRIs included pre-enhanced T1-weighted, coronal fat-Suppressed T2-weighted (FS-T2W) and enhanced T1-weighted imaging. The clinical and MRI dates were reviewed. The gold standard of SIF was based on radiologic findings, clinical data and follow-up at least 12 months.

Results

28 patients (10.8%) with 47 sites were diagnosed with SIFs, including 9 patients with unilateral SIF and 19 patients with bilateral SIFs. The median age was 60 years (range 41–72 years), and 89.3% (25/28) of patients were postmenopausal. 64.3% (18/28) of patients were symptomatic, and 53.6% of patients (15/28) had concomitant pelvic fractures. The median interval time from RT to SIFs was 10 months (range 3–34 months). For the lesion-wise analysis based on all MR images, all lesions were detected by visualizing bone marrow edema patterns, and fracture lines were detected in 64.6% (31/47) of SIFs. No soft-tissue tumors were founded. For each MRI sequence analysis, coronal FS-T2WI detected the most bone marrow edema pattern and fracture line than T1WI or enhanced T1WI.

Conclusion

SIF is a common complication in cervical cancer after radiotherapy, which has some certain clinical and MRI features. Coronal FS-T2WI may be more useful to detect and characterize these fractures than other imaging sequences.
The prevalence and phenotypic manifestations of polycystic ovary syndrome (PCOS) among infertile Sudanese women: a cross-sectional study
Authors: Elasam Alawia N. , Ahmed Mohamed A. , Ahmed Abdel B. A. , Sharif Manal E. , Abusham Abdalla , Hassan Bahaeldin , Adam Ishag
Published: May 2022

Background

Polycystic ovary syndrome (PCOS) is a global health problem associated with significant morbidity during reproductive age. Only a few published studies that address the clinical manifestations and phenotypic presentation of the disease have been conducted in Africa, including Sudan. Thus, this study aimed to evaluate the clinical and biochemical presentation of the different PCOS phenotypes among infertile Sudanese women.

Methods

A cross-sectional, descriptive study was conducted from January to December 2019. A total of 368 infertile women with PCOS (based on the Rotterdam criteria) were recruited from a fertility center in Khartoum, Sudan. Clinical, hormonal, and ultrasonographic characteristics were described and compared between the four phenotypes of PCOS.

Results

Majority (321 [87.2%]) of the women had oligo/anovulation (OA). Polycystic ovary morphology on ultrasound appeared in 236 (64.1%) women, acne in 171 (46.5%) women, acanthosis nigricans in 81 (22.0%) women, and hirsutism in 101 (27.4%) women. Phenotype D was the most prevalent among infertile Sudanese women (51.6%), followed by phenotype B (22.6%), phenotype C (18.2%), and phenotype A (7.6%). No statistical differences in the body mass index and hormonal profile between the four phenotypes were noted. Women with phenotype A were older and had high mean blood pressure, and a higher waist/hip ratio was observed among women with phenotype D.

Conclusion

Unlike the global distribution of PCOS phenotypes, Sudanese women uniquely expressed phenotype D as the most prevalent. More epidemiological studies are needed in the region due to geographical, ethnic, and genetic variations.
The effectiveness of using virtual patient educational tools to improve medical students’ clinical reasoning skills: a systematic review
Authors: Plackett Ruth , Kassianos Angelos P. , Mylan Sophie , Kambouri Maria , Raine Rosalind , Sheringham Jessica
Published: May 2022

Background

Use of virtual patient educational tools could fill the current gap in the teaching of clinical reasoning skills. However, there is a limited understanding of their effectiveness. The aim of this study was to synthesise the evidence to understand the effectiveness of virtual patient tools aimed at improving undergraduate medical students’ clinical reasoning skills.

Methods

We searched MEDLINE, EMBASE, CINAHL, ERIC, Scopus, Web of Science and PsycINFO from 1990 to January 2022, to identify all experimental articles testing the effectiveness of virtual patient educational tools on medical students’ clinical reasoning skills. Quality of the articles was assessed using an adapted form of the MERSQI and the Newcastle–Ottawa Scale. A narrative synthesis summarised intervention features, how virtual patient tools were evaluated and reported effectiveness.

Results

The search revealed 8,186 articles, with 19 articles meeting the inclusion criteria. Average study quality was moderate (M = 6.5, SD = 2.7), with nearly half not reporting any measurement of validity or reliability for their clinical reasoning outcome measure (8/19, 42%). Eleven articles found a positive effect of virtual patient tools on reasoning (11/19, 58%). Four reported no significant effect and four reported mixed effects (4/19, 21%). Several domains of clinical reasoning were evaluated. Data gathering, ideas about diagnosis and patient management were more often found to improve after virtual patient use (34/47 analyses, 72%) than application of knowledge, flexibility in thinking and problem-solving (3/7 analyses, 43%).

Conclusions

Using virtual patient tools could effectively complement current teaching especially if opportunities for face-to-face teaching or other methods are limited, as there was some evidence that virtual patient educational tools can improve undergraduate medical students’ clinical reasoning skills. Evaluations that measured more case specific clinical reasoning domains, such as data gathering, showed more consistent improvement than general measures like problem-solving. Case specific measures might be more sensitive to change given the context dependent nature of clinical reasoning. Consistent use of validated clinical reasoning measures is needed to enable a meta-analysis to estimate effectiveness.
Research supervisors’ views of barriers and enablers for research projects undertaken by medical students; a mixed methods evaluation of a post-graduate medical degree research project program
Authors: Hart Joanne , Hakim Jonathan , Kaur Rajneesh , Jeremy Richmond , Coorey Genevieve , Kalman Eszter , Jenkin Rebekah , Bowen David
Published: May 2022

Background

Medical degree programs use scholarly activities to support development of basic research skills, critical evaluation of medical information and promotion of medical research. The University of Sydney Doctor of Medicine Program includes a compulsory research project. Medical student projects are supervised by academic staff and affiliates, including biomedical science researchers and clinician-academics. This study investigated research supervisors’ observations of the barriers to and enablers of successful medical student research projects.

Methods

Research supervisors (n = 130) completed an anonymous, online survey after the completion of the research project. Survey questions targeted the research supervisors’ perceptions of barriers to successful completion of projects and sources of support for their supervision of the student project. Data were analysed by descriptive statistics and using manifest content analysis. Further quantitative investigation was made by cross-tabulation according to prior research supervision experience.

Results

Research supervisors reported that students needed both generic skills (75%) and research-based skills (71%) to successfully complete the project. The major barrier to successful research projects was the lack of protected time for research activities (61%). The assessment schedule with compulsory progress milestones enabled project completion (75%), and improved scientific presentation (90%) and writing (93%) skills. Supervisors requested further support for their students for statistics (75%), scientific writing (51%), and funding for projects (52%). Prior research supervision experience influenced the responses. Compared to novice supervisors, highly experienced supervisors were significantly more likely to want students to be allocated dedicated time for the project (P < 0.01) and reported higher rates of access to expert assistance in scientific writing, preparing ethics applications and research methodology. Novice supervisors reported higher rates of unexpected project delays and data acquisition problems (P < 0.05). Co-supervision was favoured by experienced supervisors but rejected by novice supervisors.

Conclusions

Both generic and research-related skills were important for medical student research project success. Overall, protected research time, financial and other academic support were identified as factors that would improve the research project program. Prior research supervision experience influences perceptions of program barriers and enablers. These findings will inform future support needs for projects and research supervisor training for the research supervision role.
Understanding intra- and interprofessional team and teamwork processes by exploring facility-based neonatal care in kenyan hospitals
Authors: Jepkosgei Joyline , English Mike , Adam Mary B , Nzinga Jacinta
Published: May 2022

Background

Within intensive care settings such as neonatal intensive care units, effective intra- and interprofessional teamwork has been linked to a significant reduction of errors and overall improvement in the quality of care. In Kenya, previous studies suggest that coordination of care among healthcare teams providing newborn care is poor. Initiatives aimed at improving intra- and interprofessional teamwork in healthcare settings largely draw on studies conducted in high-income countries, with those from resource-constrained low and middle countries, particularly in the context of newborn care lacking. In this study, we explored the nature of intra- and interprofessional teamwork among health care providers in newborn units (NBUs) of three hospitals in Kenya, and the professional and contextual dynamics that shaped their interactions.

Methods

This exploratory qualitative study was conducted in three hospitals in Nairobi and Muranga Counties in Kenya. We adopted an ethnographic approach, utilizing both in-depth interviews (17) and non-participant observation of routine care provision in NBUs (250 observation hours). The study participants included: nurses, nursing students, doctors, and trainee doctors. All the data were thematically coded in NVIVO 12.

Results

The nature of intra- and interprofessional teamwork among healthcare providers in the study newborn units is primarily shaped by broader contextual factors and varying institutional contexts. As a result, several team types emerged, loosely categorized as the ‘core’ team which involves providers physically present in the unit most times during the work shift; the emergency team and the temporary ad-hoc teams which involved the ‘core’ team, support staff students and mothers. The emergence of these team types influenced relationships among providers. Overall, institutionalized routines and rituals shaped team relations and overall functioning.

Conclusions

Poor coordination and the sub-optimal nature of intra-and interprofessional teamwork in NBUs are attributed to broader contextual challenges that include low staff to patient ratios and institutionalized routines and rituals that influenced team norming, relationships, and team leadership. Therefore, mechanisms to improve coordination and collaboration among healthcare teams in these settings need to consider contextual dynamics including institutional cultures while also targeting improvement of team-level processes including leadership development and widening spaces for more interaction and better communication.
Collaboration over competition? Regulatory reform and inter-organisational relations in the NHS amidst the COVID-19 pandemic: a qualitative study
Authors: Aunger Justin Avery , Millar Ross , Rafferty Anne Marie , Mannion Russell
Published: May 2022

Background

In 2021, during the COVID-19 pandemic, England’s Department of Health and Social Care (DHSC) released a White Paper outlining proposed legislative reform of the National Health Service (NHS). Key to the proposals is the shift from relationships between providers based on competition, to cooperation, as the central driver of improved performance and quality. Against this background we explore potential regulatory barriers and enablers to collaboration identified by key NHS stakeholders and assess whether the proposed policy changes are likely to deliver the desired improvement in collaborative relationships, in the context of challenges experienced during the COVID-19 pandemic.

Methods

We conducted 32 semi-structured interviews with 30 key stakeholders, taking place during the COVID-19 pandemic from Jan 2020 to May 2021. Participants were selected for their expertise regarding collaboration and were recruited purposively. Interviews were conducted online with the use of video conferencing software. The interviews were thematically analysed to identify themes. Proposals contained in the DHSC White Paper helped to structure the thematic analysis, interpretation, and reporting of the results.

Results

Requirements to compete to provide services, regulatory ability to block collaborative arrangements, lack of collaboration between providers and Clinical Commissioning Groups, and current lack of data sharing were found to hamper collaborative efforts. These issues often negatively affected collaborative relations by increasing bureaucracy and prompted leaders to attempt to avoid future collaborations. Other barriers included opaque accountability arrangements, and erosion of trust in regulators. The COVID-19 pandemic was found to foster collaboration between organisations, but some changes mandated by the new legislation may stifle further collaboration.

Conclusions

Many of the proposed legislative changes in the White Paper would help to remove existing barriers to service integration and collaboration identified by stakeholders. However, the proposed shift in the concentration of power from NHS England to the DHSC may exacerbate historically low levels of trust between providers and regulators. Many of the proposed changes fail to address endemic NHS policy issues such as chronic understaffing. Further dialogue is needed at all levels of the health and social care system to ensure future legislative changes meet the needs of all stakeholders.
ASC proneural factors are necessary for chromatin remodeling during neuroectodermal to neuroblast fate transition to ensure the timely initiation of the neural stem cell program
Authors: Theodorou Vasiliki , Stefanaki Aikaterini , Drakos Minas , Triantafyllou Dafne , Delidakis Christos
Published: May 2022

Background

In both Drosophila and mammals, the achaete-scute (ASC/ASCL) proneural bHLH transcription factors are expressed in the developing central and peripheral nervous systems, where they function during specification and maintenance of the neural stem cells in opposition to Notch signaling. In addition to their role in nervous system development, ASC transcription factors are oncogenic and exhibit chromatin reprogramming activity; however, the impact of ASC on chromatin dynamics during neural stem cell generation remains elusive. Here, we investigate the chromatin changes accompanying neural commitment using an integrative genetics and genomics methodology.

Results

We found that ASC factors bind equally strongly to two distinct classes of cis-regulatory elements: open regions remodeled earlier during maternal to zygotic transition by Zelda and less accessible, Zelda-independent regions. Both classes of cis-elements exhibit enhanced chromatin accessibility during neural specification and correlate with transcriptional regulation of genes involved in a variety of biological processes necessary for neuroblast function/homeostasis. We identified an ASC-Notch regulated TF network that includes likely prime regulators of neuroblast function. Using a cohort of ASC target genes, we report that ASC null neuroblasts are defectively specified, remaining initially stalled, unable to divide, and lacking expression of many proneural targets. When mutant neuroblasts eventually start proliferating, they produce compromised progeny. Reporter lines driven by proneural-bound enhancers display ASC dependency, suggesting that the partial neuroblast identity seen in the absence of ASC genes is likely driven by other, proneural-independent, cis-elements. Neuroblast impairment and the late differentiation defects of ASC mutants are corrected by ectodermal induction of individual ASC genes but not by individual members of the TF network downstream of ASC. However, in wild-type embryos, the induction of individual members of this network induces CNS hyperplasia, suggesting that they synergize with the activating function of ASC to consolidate the chromatin dynamics that promote neural specification.

Conclusions

We demonstrate that ASC proneural transcription factors are indispensable for the timely initiation of the neural stem cell program at the chromatin level by regulating a large number of enhancers in the vicinity of neural genes. This early chromatin remodeling is crucial for both neuroblast homeostasis as well as future progeny fidelity.
Genome of a giant isopod, Bathynomus jamesi, provides insights into body size evolution and adaptation to deep-sea environment
Authors: Yuan Jianbo , Zhang Xiaojun , Kou Qi , Sun Yamin , Liu Chengzhang , Li Shihao , Yu Yang , Zhang Chengsong , Jin Songjun , Xiang Jianhai , Li Xinzheng , Li Fuhua
Published: May 2022

Background

The deep-sea may be regarded as a hostile living environment, due to low temperature, high hydrostatic pressure, and limited food and light. Isopods, a species-rich group of crustaceans, are widely distributed across different environments including the deep sea and as such are a useful model for studying adaptation, migration, and speciation. Similar to other deep-sea organisms, giant isopods have larger body size than their shallow water relatives and have large stomachs and fat bodies presumably to store organic reserves. In order to shed light on the genetic basis of these large crustaceans adapting to the oligotrophic environment of deep-sea, the high-quality genome of a deep-sea giant isopod Bathynomus jamesi was sequenced and assembled.

Results

B. jamesi has a large genome of 5.89 Gb, representing the largest sequenced crustacean genome to date. Its large genome size is mainly attributable to the remarkable proliferation of transposable elements (84%), which may enable high genome plasticity for adaptive evolution. Unlike its relatives with small body size, B. jamesi has expanded gene families related to pathways of thyroid and insulin hormone signaling that potentially contribute to its large body size. Transcriptomic analysis showed that some expanded gene families related to glycolysis and vesicular transport were specifically expressed in its digestive organs. In addition, comparative genomics and gene expression analyses in six tissues suggested that B. jamesi has inefficient lipid degradation, low basal metabolic rate, and bulk food storage, suggesting giant isopods adopt a more efficient mechanism of nutrient absorption, storage, and utilization to provide sustained energy supply for their large body size.

Conclusions

Taken together, the giant isopod genome may provide a valuable resource for understanding body size evolution and adaptation mechanisms of macrobenthic organisms to deep-sea environments.
The interaction between long non-coding RNA LINC01564 and POU2F1 promotes the proliferation and metastasis of gastric cancer
Authors: Wang Jixu , Hou Futao , Tang Lusheng , Xiao Ke , Yang Tengfei , Wang Zhiqiang , Liu Gu
Published: May 2022

Background

An increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) serve as key regulators in tumor development and progression. However, only a few lncRNAs have been functionally characterized in gastric cancer (GC).

Methods

Bioinformatics analysis was conducted to find lncRNAs that are associated with GC metastasis. RNA FISH, RIP, and RNA pull down assays were used to study the complementary binding of LINC01564 complementary to the 3′UTR of transcription factor POU2F1. The transcription activation of LINC01564 by POU2F1 as a transcription factor was examined by ChIP assay. In vitro assays such as MTT, cell invasion assay, and clonogenic assay were conducted to examined the impacts of LINC01564 and POU2F1 on GC cell proliferation and invasion. Experiments in vivo were performed to access the impacts of LINC01564 and POU2F1 on GC metastasis.

Results

The results showed that LINC01564 complementary bound to the 3′UTR of POU2F1 to form an RNA duplex, whereby stabilizing POU2F1 mRNA and increasing the enrichment in cells. The level of LINC01564 was also increased by POU2F1 through transcription activation. In vitro assays showed that LINC01564 promoted the proliferation, invasion and migration of GC cells through increasing POU2F1. In vivo experiments indicate the promotion of GC proliferation and metastasis by the interaction between LINC01564 and POU2F1.

Conclusion

Taken together, our results indicate that the interaction between LINC01564 and POU2F1 promotes the proliferation, migration and invasion of GC cells.
St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis
Authors: Cao Rong-chang , Yang Wan-jun , Xiao Wang , Zhou Lei , Tan Jie-hui , Wang Meng , Zhou Zhi-tao , Chen Huo-ji , Xu Jia , Chen Xue-mei , Jin Yang-chen , Lin Jia-yu , Zeng Jun-ling , Li Shu-ji , Luo Min , Hu Guo-dong , Jin Jin , Yang Xiao-bing , Huo Da , Zhou Jie , Zhang Guo-wei
Published: May 2022

Background

Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP.

Methods

Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13−/− mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model.

Results

The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling.

Conclusion

St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.
VCP interaction with HMGB1 promotes hepatocellular carcinoma progression by activating the PI3K/AKT/mTOR pathway
Authors: Pu Zhangya , Duda Dan G. , Zhu Yuanyuan , Pei Siya , Wang Xiaofang , Huang Yan , Yi Panpan , Huang Zebing , Peng Fang , Hu Xingwang , Fan Xuegong
Published: May 2022

Background

Hepatocellular carcinoma (HCC) is the most common pathological type of liver cancer. Valosin-containing protein (VCP) is a member of the AAA-ATPase family associated with multiple molecular functions and involved in tumor metastasis and prognosis. However, the role of VCP in HCC progression is still unclear.

Methods

We examined the expression of VCP in HCC using the RNA sequencing and microarray data from public databases and measured it in clinical samples and cell lines by western blot, and immunohistochemistry (IHC). We also evaluated the correlation between VCP and clinical features. The VCP-interacting proteins were identified by co-immunoprecipitation combined with mass spectrometry (CoIP/MS). The underlying molecular mechanisms were investigated using in vitro and in vivo models of HCC.

Results

We found that VCP expression is significantly increased in tumor tissues and is associated with advanced TNM stages and poorer prognosis in HCC patients. In vitro analyses revealed that VCP overexpression promoted HCC cell proliferation, migration, and invasion via PI3K/AKT/mTOR pathway activation. Conversely, VCP knockdown resulted in the reverse phenotypes. In vivo studies indicated that up-regulated VCP expression accelerated tumor growth in a subcutaneous HCC model. The D1 domain of VCP and A box of HMGB1 were identified as the critical regions for their interaction, and D1 area was required for the tumor-promoting effects induced by VCP expression. VCP enhanced the protein stability of HMGB1 by decreasing its degradation via ubiquitin–proteasome process. Inhibition of HMGB1 markedly attenuated VCP-mediated HCC progression and downstream activation of PI3K/AKT/mTOR signals.

Conclusion

Collectively, these findings demonstrate that VCP is a potential prognostic biomarker in HCC and exhibits oncogenic roles via PI3K/AKT/mTOR pathway activation. HMGB1 played an essential role in VCP-mediated HCC progression, indicating that VCP and HMGB1 are potential therapeutic targets in human HCC.
5-fluorouracil treatment of patient-derived scaffolds from colorectal cancer reveal clinically critical information
Authors: Salerno Simona , Ståhlberg Anders , Holdfeldt André , Bexe Lindskog Elinor , Landberg Göran
Published: May 2022

Background

Colorectal cancer is a commonly diagnosed cancer worldwide. Unfortunately, many patients do not respond to standard chemotherapy treatments and develop disease relapse and metastases. Besides cancer cell specific genetic changes, heterogeneity in the tumor microenvironment contribute to the clinical presentation of the disease and can potentially also influence drug resistance. By using a recently developed patient-derived scaffold method monitoring how a standardized reporter cancer cell line adapts to various microenvironments treated with chemotherapy, we wanted to clarify how individual patient specific microenvironments influence the chemotherapy response in colorectal cancer.

Methods

Surgically resected colorectal cancer specimens from 89 patients were decellularized to produce patient-derived scaffold, which were seeded with HT29 cells, cultured for 3 weeks, and treated with 5-fluorouracil. Gene expression changes of adapted and treated HT29 cells were monitored by qPCR and compared with clinical parameters including disease-free survival.

Results

The effects of 5-fluorouracil treatment varied between different patient-derived scaffold, but generally induced a reduced expression of proliferation genes and increased expression of pluripotency and epithelial-to-mesenchymal transition genes. Interestingly, patient-derived scaffold cultures obtained from patients with disease recurrences showed a significantly less pronounced anti-proliferative effect of 5-fluorouracil and more pronounced increase of pluripotency, with MKI67 and POU5F1 being among the most significant genes linked to disease relapse in colorectal cancer.

Conclusions

Colorectal patient-derived scaffold can decode clinically relevant tumor microenvironmental influence of 5-fluorouracil treatment effects opening up for optimized precision medicine in colorectal cancer treatment.
Single-cell landscape of immunocytes in patients with extrahepatic cholangiocarcinoma
Authors: Xu Lei , Lu Yun , Deng Zhengdong , Li Xiangyu , Shi Yuanxin , Zhao Kai , Yao Wei , Wang Jianming
Published: May 2022

Background

The intricate landscape of immunocytes in the tumor microenvironment (TME) is fundamental to immunotherapy but notably under-researched in extrahepatic cholangiocarcinoma (ECCA).

Methods

Single-cell RNA sequencing technology was conducted to make an in-depth analysis of immunocytes from matched tumor tissues, paratumor tissues and peripheral blood from ECCA patients. The potential cellular interactions between two cell populations were analyzed with software CellPhoneDB (v2.1.7).

Results

We obtained 13526 cells and characterized the transcriptomes and heterogeneity of different clusters and subclusters of immunocytes from ECCA, including CD4+ T cells, CD8+ T cells, B cells and myeloid immunocytes. We observed the rarely described immunocyte subclusters "intermediate" exhausted CD8+ T (CD8+ Tex) cells and “nonclassic” plasmacytes (CD27+ CD138+ CD38−). In addition, we identified potential immunotherapy targets, for example, ACP5, MAGEH1, TNFRSF9 and CCR8 for Tregs and MT1 for CD8+ Tex cells. We also found strong cellular interactions among Treg cells, M2 macrophages and CD8+ Tex cells through ligand–receptor analysis, implying that potential cellular cross-linkage promoted the immunosuppressive nature of the TME.

Conclusions

In a word, our study illuminated the components of the TME and revealed potential cellular interactions at the individual cellular level in ECCA, we aimed to provide a new perspective for further immunological studies and immunotherapy of ECCA.
Correction to: Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats
Authors: Takeda Tomoki , Yamano Shotaro , Goto Yuko , Hirai Shigeyuki , Furukawa Yusuke , Kikuchi Yoshinori , Misumi Kyohei , Suzuki Masaaki , Takanobu Kenji , Senoh Hideki , Saito Misae , Kondo Hitomi , Daghlian George , Hong Young-Kwon , Yoshimatsu Yasuhiro , Hirashima Masanori , Kobashi Yoichiro , Okamoto Kenzo , Kishimoto Takumi , Umeda Yumi
Published: May 2022

Graphic abstract
Observation of curative effect on meridian theory-based extracorporeal shock wave therapy for non-specific low back pain: study protocol for a randomized controlled trial
Authors: Fan Yongfu , Liu Feilai , Li Mengna , Ruan Xiaodi , Wu Mingli , Su Kaiqi , Gao Jing , Feng Xiaodong
Published: May 2022

Background

Non-specific low back pain (NLBP) is a major global socioeconomic burden, and the prevalence of NLBP is still on the rise. At present, there is no ideal drug to cure this disease. This may be the reason why patients often use complementary therapies. Among them, extracorporeal shock wave therapy (ESWT) has gradually received more attention and has become the main treatment method for NLBP. The purpose of this study is to provide scientific evidence for the effect and safety of meridian theory-based ESWT on NLBP.

Objective

This study aims to evaluate the effect and safety of meridian theory-based ESWT on NLBP. This study will also provide more high-quality experimental evidence for the clinical application of meridian theory-based ESWT for the treatment of NLBP in future.

Methods

The study design is a single-blind, multi-center, randomized controlled trial. 66 patients with NLBP, aged 18 to 60 years, will be randomly divided into two groups: the experimental group (N = 33), which will receive meridian theory-based ESWT application, and the control group (N = 33) which will receive conventional ESWT treatment. These two applications will be carried out twice a week for two weeks. The primary outcome will be the Visual Analog Scale (VAS), and the secondary outcomes will be Oswestry Disability Index (ODI), Surface Electromyography (sEMG), and Patient Health Questionnaire-15 (PHQ-15). All outcomes will be evaluated at baseline and after the intervention (7 days, 14 days).

Discussion

Results of this trial will contribute to providing rigorous clinical evidence for the efficacy and security of meridian theory-based ESWT for NLBP.

Trial registration: Chinese Clinical Trial Registry, ChiCTR2100051049. Registered on 10 September 2021, http://www.chictr.org.cn/showproj.aspx?proj=46316.
Effect of human follicle-stimulating hormone on immunomodulatory function of decidual mesenchymal stem cells by reducing interleukin-6 levels
Authors: He Yi-bo , Zhang Li , Zhou Lin-li , Chen Yi-min , Lu Jia-hong , Chen Jie , Liu Yong-lin
Published: May 2022

Objective

Women with an elevated basal FSH indicate diminished ovarian reserve and reduced oocyte and embryo numbers. DMSCs are likely to be involved in immune tolerance of pregnancy maintenance. We investigate the effect of follicle-stimulating hormones on the immunomodulatory functions of DMSCs.

Methods

DMSCs were primary cultured from decidual tissue. Pretreated DMSCs with mitomycin C, combined with CD4+ T lymphocytes, DMSCs + CD4+T co-culture system was established. Different physiological dose FSH (3 ng/ml,10 ng/ml,30 ng/ml,100 ng/ml) were used to co-culture system. Cytokines (IFN-γ, IL-2, IL-4, IL-6, IL-10, TNF-α) and other proteins (FSHR, MyD88) were measured.

Results

Compared with the control group (FSH (0 ng/mL) + CD4+T + DMSCs), the FSH concentration was 10, 30, and 100 ng/ml, IL-6 levels were significantly reduced (P < 0.05). IL-6, MyD88 protein expression was remarkably decreased (P < 0.05).

Conclusion

FSH/FSHR could negatively regulate the immunosuppressive function of DMSCs by reducing secretion of IL-6 levels through MyD88 pathways, but upstream and downstream signalling pathways require further validation.
A nationwide survey on the implementation of infection prevention and control components in 1442 hospitals in the Republic of Korea: comparison to the WHO Infection Prevention and Control Assessment Framework (IPCAF)
Authors: Jeong Yoolwon , Joo Hyeyoung , Bahk Hyunjung , Koo Hyunsuk , Lee Hyungmin , Kim Kinam
Published: May 2022

Background

The current SARS-CoV-2 pandemic continues to underscore the inadequacy of infection prevention and control (IPC) and the importance of its sound establishment in healthcare facilities. The Infection Prevention and Control Assessment Framework (IPCAF) by the World Health Organization allows systematic assessment of IPC capacity in healthcare facilities and has been applied in many national-level surveys. This study aims to assess the IPC capacity of Korean hospitals as well as their strengths and pitfalls by analyzing the results of the first government-led nationwide IPC survey in comparison to the IPCAF frame.

Methods

The Korean National Infection Prevention and Control Survey (KNIPCS) was conducted from February to March 2018. The survey questionnaire for KNIPCS was developed through a series of expert consultations and a round of pre-testing in two randomly selected hospitals. The survey questionnaire was distributed to a total of 2108 hospitals. Although the survey preceded the release of IPCAF, its contents complied with IPCAF to a large extent, allowing exploration of its results with regards to IPCAF.

Results

All tertiary hospitals and 96.5% of general hospitals had implemented IPC teams, whereas the percentage was lower for long-term care hospitals (6.3%). A similar trend was observed for IPC surveillance and monitoring activities across hospital types. The percentage of interactive IPC training was lower than 30% in all hospital groups. Disinfection was frequently monitored in all hospital types (e.g. 97.3% in general hospitals and 85.3% in long-term care hospitals). However, activities regarding antimicrobial resistance, such as multi-drug resistant pathogen screening, were weak in hospitals (25%) and long-term care hospitals (25%), compared to tertiary hospitals (83.3%) and general hospitals (57.7%).

Conclusions

In general, essential IPC structures, such as IPC teams and programs, were well in place in most tertiary and general hospitals in Korea. These hospital groups also actively conducted various IPC activities. As most previous legislative and multimodal policy measures have targeted these hospital groups, we speculate that future policy efforts should encompass long-term care hospitals and smaller-sized hospitals to strengthen the IPC capacity of these hospital groups. Efforts should also be put forth to promote IPC training and antimicrobial activities.
Immunogenicity and safety of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine: a systematic review
Authors: Lv Jingjing , Wu Hui , Xu Junjie , Liu Jiaye
Published: May 2022

Background

Heterologous prime-boost with ChAdOx1 nCoV-19 vector vaccine (ChAd) and a messenger RNA vaccine (BNT or mRNA-1273) has been widely facilitating mass coronavirus disease 2019 (COVID-19) immunisation. This review aimed to synthesize immunogenicity and reactogenicity of heterologous immunisations with ChAd and BNT (mRNA-1273) vaccine compared with homologous ChAd or BNT (mRNA-1273) immunisation.

Methods

PubMed, Web of Science, and Embase databases were searched from inception to March 7, 2022. Immunogenicity involving serum antibodies against different SAS-CoV-2 fragments, neutralizing antibody, or spike-specific T cells response were compared. Any, local and systemic reactions were pooled by meta-analysis for comparison.

Results

Of 14,571 records identified, 13 studies (3024 participants) were included for analysis. Compared with homologous BNT/BNT vaccination, heterologous ChAd/BNT schedule probably induced noninferior anti-spike protein while higher neutralizing antibody and better T cells response. Heterologous ChAd/BNT (mRNA-1273) immunisation induced superior anti-spike protein and higher neutralizing antibody and better T cells response compared with homologous ChAd/ChAd vaccination. Heterologous ChAd/BNT (mRNA-1273) had similar risk of any reaction (RR = 1.30, 95% CI: 0.86−1.96) while higher risk of local reactions (RR = 1.65, 95% CI: 1.27−2.15) and systemic reactions (RR = 1.49, 95% CI: 1.17−1.90) compared with homologous ChAd/ChAd vaccination. There was a higher risk of local reactions (RR = 1.16, 95% CI: 1.03−1.31) in heterologous ChAd/BNT (mRNA-1273) vaccination compare with homologous BNT/BNT but a similar risk of any reaction (RR = 1.03, 95% CI: 0.79−1.34) and systemic reactions (RR = 0.89, 95% CI: 0.60−1.30).

Conclusions

Heterologous ChAd/BNT schedule induced at least comparable immunogenicity compared with homologous BNT/BNT and better immunogenicity compared with homologous ChAd/ChAd vaccination. The synthetical evidence supported the general application of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines.

Graphical Abstract
Potential risk of colonization of Bulinus globosus in the mainland of China under climate change
Authors: Wang Xinyao , Juma Saleh , Li Wei , Suleman Mchanga , Muhsin Mtumweni Ali , He Jian , He Mingzhen , Xu Dacheng , Zhang Jianfeng , Bergquist Robert , Yang Kun
Published: May 2022

Background

Bulinus globosus, the main intermediate snail host of Schistosoma haematobium. The increased contacts between Africa and China could even lead to large-scale dissemination of B. globosus in China. Temperature is the key factor affecting fresh-water snail transmission. This study predicted potential risk of colonization of B. globosus in the mainland of China under climate change.

Methods

We investigated minimum and maximum temperatures for B. globosus eggs, juveniles and adult snails kept under laboratory conditions to find the most suitable range by pinpointing the median effective temperatures (ET50). We also assessed the influence of temperature on spawning and estimated the accumulated temperature (AT). The average air temperatures between 1955 and 2019 in January and July, the coldest and hottest months in China, respectively, were collected from national meteorological monitoring stations and investigated in a geographic information system (GIS) using empirical Bayesian Kriging to evaluate the theoretical possibility for distribution of B. globosus in southern China based on temperature.

Results

The effective minimum temperature (ET50min) for eggs, juveniles, adult snails and spawning were 8.5, 7.0, 7.0, 14.9 °C, respectively, with the corresponding maximum values (ET50max) of 36.6, 40.5, 40.2 and 38.1 °C. The AT was calculated at 712.1 ± 64.9 °C·d. In 1955, the potential B. globosus distribution would have had a northern boundary stretching from the coastal areas of Guangdong Province and Guangxi Autonomous Region to southern Yunnan Province. Since then, this line has gradually moved northward.

Conclusions

Annual regeneration of B. globosus can be supported by the current climate conditions in the mainland of China, and a gradual expansion trend from south to north is shown in the study from 2015 to 2019. Thus, there is a potential risk of colonization of B. globosus in the mainland of China under climate change.

Graphical Abstract