bluuebunny/crossref_metadata_2025 huggingface dataset:
Recruitment and retention into longitudinal health research from an adolescent perspective: a qualitative study
Authors: Jong Stephanie T. , Stevenson Rebecca , Winpenny Eleanor M. , Corder Kirsten , van Sluijs Esther M. F.
Published: January 2023

Background

High quality longitudinal studies investigating changes in health behaviours over the transition into early adulthood are critical. However, recruiting and retaining adolescents is challenging. This study explored adolescents’ perspectives of signing up to and continuing involvement in a hypothetical longitudinal health research study.

Methods

Forty-eight individuals (15-20y) participated in nine in-person focus groups about recruitment and retention in research. Participants were (a) school students in the last year of compulsory school (Year 11, 15-16y), (b) school/college students in Sixth Form (Year 13, 17-18y), (c) Further Education students studying after secondary education, but not higher education (16-18y) and (d) young adults not in education, employment, or training (18-20y) across England. Thematic analysis resulted in seven themes.

Results

Driving factors for sign-up included social connection e.g., joining with peer groups, personalised feedback, and incentives, primarily financial. Key barriers were lack of interest, the perception of commitment, and timing of recruitment. Young people preferred recruitment processes via social media with messages tailored to their motivations, monthly data collection of maximally 20–30 min, and hybrid data collection with some in-person contact with a consistent, non-judgemental researcher. The provision of autonomy, choice, and financial incentives were perceived to promote retention.

Conclusions

Adolescent recruitment and retention strategies need to align with contemporary interests and motivations. Studies should involve adolescents early to develop a planned, systematic approach to participant sign-up and follow-up. Effective and ineffective recruitment and retention strategies should be reported as part of study findings. Future research should trial how perceived barriers to study engagement can be overcome.
Understanding illness experiences of patients with primary sclerosing cholangitis: a qualitative analysis within the SOMA.LIV study
Authors: Loesken Caroline , Maehder Kerstin , Buck Laura , Hartl Johannes , Löwe Bernd , Schramm Christoph , Toussaint Anne
Published: January 2023

Background

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease with a largely unpredictable course. Due to limited treatment options, individuals may for many years suffer from distressing symptoms and the emotional burden of an uncertain future. The need to shift from cure to care of PSC has spurred an interest into patients’ health-related quality of life. Qualitative research in this context remains scarce. Hence, this study aimed to enrich the clinical understanding about the lived experience of PSC through a qualitative approach.

Methods

A total of 20 patients with PSC were recruited at a specialist centre for autoimmune liver disease in Germany and engaged in semi-structured telephone-based interviews between March and June 2022. Verbatim transcripts were interpreted using inductive thematic analysis.

Results

An overarching concept of ‘a wave-like experience’ was formulated to illustrate the dual and shifting nature of living with PSC. Reflecting upon this central idea, three major themes were generated to address important aspects of participants’ illness experiences: ‘Invisible presence’ focused on perceptions of suffering from a seemingly hidden illness that periodically reveals itself through specific trigger events. ‘Embracing the threat’ captured the psycho-emotional response shift to this chronic disease from a predominantly negative to a coping-oriented pattern with regular setbacks. ‘Between control and constraints’ uncovered restrictions that PSC enforces onto patients’ lives and their desire for controllability.

Conclusions

The present study provides an in-depth look at the fluctuating tensions arising from a life with PSC. Insights on perceived invisibility, disease-related triggers of emotional distress and the complexity behind self-management highlight opportunities for enhanced clinical support of this patient group.
Comparison of adverse pregnancy and birth outcomes using archival medical records before and during the first wave of the COVID-19 pandemic in Kinshasa, Democratic Republic of Congo: a facility-based, retrospective cohort study
Authors: Arena Patrick J. , Dzogang Camille , Gadoth Adva , Nkamba Dalau Mukadi , Hoff Nicole A. , Kampilu David , Beia Michael , Wong Hui-Lee , Anderson Steven A. , Kaba Didine , Rimoin Anne W.
Published: January 2023

Background

Little research has been conducted on the impact of the coronavirus disease 2019 (COVID-19) pandemic on either birth outcomes or the ability of archival medical records to accurately capture these outcomes. Our study objective is thus to compare the prevalence of preterm birth, stillbirth, low birth weight (LBW), small for gestational age (SGA), congenital microcephaly, and neonatal bloodstream infection (NBSI) before and during the first wave of the COVID-19 pandemic in Kinshasa, Democratic Republic of Congo (DRC).

Methods

We conducted a facility-based retrospective cohort study in which identified cases of birth outcomes were tabulated at initial screening and subcategorized according to level of diagnostic certainty using Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) definitions. Documentation of any birth complications, delivery type, and maternal vaccination history were also evaluated. The prevalence of each birth outcome was compared in the pre-COVID-19 (i.e., July 2019 to February 2020) and intra-COVID-19 (i.e., March to August 2020) periods via two-sample z-test for equality of proportions.

Results

In total, 14,300 birth records were abstracted. Adverse birth outcomes were identified among 22.0% and 14.3% of pregnancies in the pre-COVID-19 and intra-COVID-19 periods, respectively. For stillbirth, LBW, SGA, microcephaly, and NBSI, prevalence estimates were similar across study periods. However, the prevalence of preterm birth in the intra-COVID-19 period was significantly lower than that reported during the pre-COVID-19 period (8.6% vs. 11.5%, p < 0.0001). Furthermore, the level of diagnostic certainty declined slightly across all outcomes investigated from the pre-COVID-19 to the intra-COVID-19 period. Nonetheless, diagnostic certainty was especially low for certain outcomes (i.e., stillbirth and NBSI) regardless of period; still, other outcomes, such as preterm birth and LBW, had moderate to high levels of diagnostic certainty. Results were mostly consistent when the analysis was focused on the facilities designated for COVID-19 care.

Conclusion

This study succeeded in providing prevalence estimates for key adverse birth outcomes using GAIA criteria during the COVID-19 pandemic in Kinshasa, DRC. Furthermore, our study adds crucial real-world data to the literature surrounding the impact of the COVID-19 pandemic on maternal and neonatal services and outcomes in Africa.
Effect modification by developmental stage of embryos on the association between late follicular phase progesterone elevation and live birth in fresh transfers
Authors: Li Fei , Cai He , Tian Li , Bai Haiyan , Shi Juanzi
Published: January 2023

Background

Late follicular phase progesterone elevation (LFPE) during ovarian stimulation is associated with reduced live birth rates (LBRs) after cleavage-stage embryo transfer. However, due to better synchronization with a stimulated endometrium, prior studies shown that LFPE had no effect on transferring embryos at blastocyst stage. The study aim to exam whether the developmental stage of embryos and serum progesterone levels on the day of human chorionic gonadotropin (hCG) administration jointly affect the odds of live birth in fresh fresh IVF/intracytoplasmic sperm injection (ICSI) cycles. 

Methods

The single-center retrospective cohort study included a total of 4,471 fresh embryo transfer cycles with 2,342 at cleavage stage versus 2,129 at blastocyst stage. Patients underwent IVF/ICSI with ovarian stimulation in gonadotropin-releasing hormone antagonist protocol. The serum progesterone level was examined both as a continuous variable and as a categorical variable by quartiles. Analysis was performed using the generalized estimating equations framework and multivariate regression models.

Results

LBRs were inversely associated with progesterone as a continuous variable on the day of hCG in both the cleavage-stage (crude OR 0.87, 95%CI 0.73–1.03; adjusted OR 0.80, 95% CI 0.65–0.98) and the blastocyst-stage (crude OR 0.66, 95%CI 0.56–0,78; adjusted OR 0.61, 95%CI 0.50–0.73) groups. The interaction testing was highly significant (P = 0.018) indicating an effect modifying role of stage of embryos transferred on the association of pregesterone values with the LBRs in fresh cycles. A similar pattern for a greater reduction in ORs for live birth in cycles with blastocysts transfer was also observed when progesterone was analyzed by interquartile ranges. The findings remained unchanged in subgroup analysis stratified by types of ovarian response.

Conclusions

In fresh cycles, detrimental effect of late follicular phase progesterone elevation on live birth was more prominent in blastocyst-stage group compared with that in clevaged-stage group.
De novo variations of ANK1 gene caused hereditary spherocytosis in two Chinese children by affecting pre-mRNA splicing
Authors: Wang Yang , Huang Lan , Zhu Yao , An Xizhou , Li Jiacheng , Zhen Jiangwei , Yu Jie
Published: January 2023

Background and aims

Hereditary spherocytosis (HS) is one of the most common hereditary haemolytic disorders. Here, two unrelated families with the probands displaying typical manifestations of HS were enrolled. Our study aimed to characterize the effect of two novel variants in HS patients on gene splicing to help minimize the rate of misdiagnosis of HS and enhance clinicians’ understanding of the disease.

Participants and methods

A retrospective review was conducted. Peripheral blood samples were collected from all the family members, and genomic DNA was extracted for genetic diagnostics. First, high-throughput sequencing technology was used for the preliminary screening of candidate causative variants. Thereafter, the variants were verified via Sanger sequencing. Furthermore, a pathogenicity analysis of the detected variants was performed including in silico prediction and in vitro experiments. We constructed matched wild-type and mutant-type minigene plasmid of ANK1 based on HEK293T cells to address the effects of variants on mRNA splicing.

Results

The c.1305 + 2 T > A (family1) and c.1305 + 2del (family2) variants were detected in the ANK1 gene. These two de novo mutations described by us which have not been reported prior to this study. Moreover, the validation results of splicing reporter systems revealed that the intronic mutations resulted in abnormal pre-mRNA splicing. Specifically, the minigene plasmid expressing the c.1305 + 2 T > A variant transcribed the two aberrant transcripts: r.1305_1306ins1305 + 1_1305 + 229 and r.1305_1306ins1305 + 1_1305 + 552. The minigene plasmid expressing c.1305 + 2del transcribed the two aberrant transcripts: r.1305_1306ins1305 + 1_1305 + 228 and r.1305_1306ins1305 + 1_1305 + 551.

Conclusion

The two de novo variants identified in the ANK1 gene were the genetic etiology of the probands with HS in our study. Our findings further enrich the HS genotype database and provide a basis for genetic counselling and molecular diagnosis.
The application value of mean red blood cell volume and red blood cell volume distribution width combined with total serum bilirubin in the early screening of neonatal hemolytic disease
Authors: Lin Hongxing , Luo Pingxiang , Liu Chen , Lin Xiaosong , Que Chengwen , Zhong Wenhui
Published: January 2023

Background

The hemolytic nature of hemolytic disease of the newborn (HDN) is described as the abnormal destruction and decomposition of red blood cells, causing heterogeneous manifestations such as abnormal red blood cell volume and morphology. Mean corpuscular volume (MCV) and red blood cell volume distribution width (RDW) are commonly used parameters related to red blood cell volume. Total serum bilirubin (TSB) is routinely monitored among newborns. This study aims to explore the value of MCV and RDW, combined with TSB, to improve the efficiency of HDN diagnosis.

Methods

Three hundred eighty-eight children with HDN and 371 children with non-HDN pathological jaundice who were diagnosed and treated in the neonatal department of our hospital from January 2019 to December 2020 were included in the study. Clinical data collected include examination results of laboratory indicators, such as MCV, coefficient of variation of red blood cell volume distribution width (RDW-CV), standard deviation of red blood cell volume distribution width (RDW-SD), and TSB. The differences in the indicators between the two groups of children were retrospectively analyzed.

Results

1) The detection rate of HDN in children in the early group was higher than that in the late group (P < 0.001). 2) The early-stage group had lower TSB levels and higher values of MCV, RDW-CV and RDW-SD (P < 0.001). Compared with the children in the non-HDN group, the indices in the HDN group were higher in the early stage (P < 0.001). 3) In the early stage, the TSB, MCV, RDW-CV, and RDW-SD were positively correlated with the diagnosis of HDN (P < 0.001). Early monitoring of TSB, MCV, RDW-CV and RDW-SD was valuable for HDN detection, the area under the curve (AUC) was 0.729, 0.637, 0.715, and 0.685, respectively (P < 0.001). 4) After a binary logistic analysis at TSB > 163.3 μmol/L, MCV > 96.35fL, and RDW-CV > 16.05%, the diagnosis rate of HDN increased (P < 0.001). The AUC of the HDN detected using the combined indicators was 0.841.

Conclusion

At MCV > 96.35fL or RDW-CV > 16.05%, children with jaundice in three days of birth (especially children with TSB > 163.3 μmol/L) should be screened for HDN. A combination of TSB, MCV, and RDW-CV can improve the early detection rate of HDN, contribute to reduce the readmission rate and risk of hyperbilirubinemia.
Predictors of time to first symptomatic recovery of major depressive disordered patients: a case study at Jimma University Medical Center
Authors: Asefa Ketema Zerihun , Bedada Tadele Degefa , Fufa Jaleta Abdisa , Gari Firomsa Shewa , Gelcho Gurmessa Nugussu , Akessa Geremew Muleta
Published: January 2023

Background

Major Depressive Disorder is one of the most common mental disorders, and it is the main cause of disability worldwide with a prevalence ranging from 7 to 21%.

Objective

The goal of this study was to predict the time it took for patients with severe depressive disorders at Jimma University Medical Center to experience their initial symptomatic recovery.

Study design

The researchers utilized a prospective study design.

Methods

Patients with major depressive disorder were followed up on at Jimma University Medical Center from September 2018 to August 2020 for this study. The Gamma and Inverse Gaussian frailty distributions were employed with Weibull, Log-logistic, and Log-normal as baseline hazard functions. Akaike Information Criteria were used to choose the best model for describing the data.

Results

This study comprised 366 patients, with 54.1% of them experiencing their first symptomatic recovery from a severe depressive disorder. The median time from the onset of symptoms to symptomatic recovery was 7 months. In the study area, there was a clustering effect in terms of time to first symptomatic recovery from major depressive disorder. According to the Log-normal Inverse-Gaussian frailty model, marital status, chewing khat, educational status, work status, substance addiction, and other co-variables were significant predictors of major depressive disorder (p-value < 0.05).

Conclusion

The best model for describing the time to the first symptomatic recovery of major depressive disorder is the log-normal Inverse-Gaussian frailty model. Being educated and working considerably were the variables that reduces the time to first symptomatic recovery from major depressive disorder; whereas being divorced, chewing khat, substance abused and other co-factors were the variables that significantly extends the time to first symptomatic recovery.
Psychosocial work stress and parent-child bonding during the COVID-19 pandemic: clarifying the role of parental symptoms of depression and aggressiveness
Authors: Koerber Mirjam I. , Mack Judith T. , Seefeld Lara , Kopp Marie , Weise Victoria , Starke Karla Romero , Garthus-Niegel Susan
Published: January 2023

Background

Parental work stress and impaired mental health seem to have intensified during the current COVID-19 pandemic. Both can have a negative impact on parent-child bonding: psychosocial work stress in the course of a spillover effect from work to family and symptoms of impaired mental health as part of a crossover effect from parent to child. This potentially affects the child’s development in the long term.

Method

This cross-sectional study examined the relationship between psychosocial work stress and parent-child bonding during the early COVID-19 pandemic (May–June 2020). Symptoms of depression and aggressiveness were considered as mediators of this relationship. The sample consisted of employees in Eastern Germany (n = 380; 42.9% mothers, 57.1% fathers), aged 24–55 years, with children aged 0–36 months.

Results

In the total sample, an association was only found after adjusting for potential confounders, indicating that higher psychosocial work stress is associated with weaker bonding between the parent and child (β = 0.148, p = .017, 95% CI [0.566, 5.614]). The separate analyses for mothers and fathers did not reveal a statistically significant relationship between psychosocial work stress and parent-child bonding. In the total sample, the higher the psychosocial work stress was, the higher were the parental symptoms of depression (β = 0.372, p < .001, 95% CI [3.417, 5.696]) and aggressiveness β = 0.254, p < .001, 95% CI [1.008, 3.208]). The mental health symptoms in turn were related to weaker parent-child bonding (symptoms of depression β = 0.320, p < .001, 95% CI [0.345, 0.749]; symptoms of aggressiveness β = 0.394, p < .001, 95% CI [0.697, 1.287]). The results furthermore suggested that parental mental health symptoms mediate the association between psychosocial work stress and parent-child bonding (symptoms of depression, ab = 2.491, 95% CI [1.472, 3.577] and of aggressiveness, ab = 2.091, 95% CI [1.147, 3.279]). The mediation effect was also found in the separate analyses for the mothers and fathers.

Discussion

The results of this study during the early COVID-19 pandemic in Germany highlight the importance of prevention as well as intervention measures in relation to psychosocial work stress that may play a debilitating role in the context of family relationships. In addition, the results suggest that both employers and employees should be made aware of the importance of psychosocial work stress, as it can have a negative impact on mental health, which in turn may have a major influence on family relationships.
The roles of risk perception, negative emotions and perceived efficacy in the association between COVID-19 infection cues and preventive behaviors: a moderated mediation model
Authors: Meng Guangteng , Li Qi , Yuan Xiaoyan , Zheng Ya , Hu Kesong , Dai Bibing , Liu Xun
Published: January 2023

Preventive behaviors during the COVID-19 pandemic are especially critical to the protection of individuals whose family members or acquaintances have been infected. However, limited research has explored the influence of infection cues on preventive behaviors. This study proposed an interaction model of environment-cognitive/affective-behavior to elucidate the mechanism by which infection cues influence preventive behaviors and the roles of risk perception, negative emotions, and perceived efficacy in that influence. To explore the relationships among these factors, we conducted a cross-sectional online survey in 34 provinces in China during the first wave of the COVID-19 pandemic. A total of 26,511 participants responded to the survey, and 20,205 valid responses (76.2%) were obtained for further analysis. The moderated mediation results show that infection cues positively predicted preventive behaviors in a manner mediated by risk perception and negative emotions. Moreover, perceived efficacy moderated the influence of infection cues not only on preventive behaviors but also on risk perception and negative emotions. The higher the perceived efficacy, the stronger these influences were. These findings validated our model, which elucidates the mechanisms underlying the promoting effect of infection cues on preventive behaviors during the initial stage of the COVID-19 pandemic. The implications of these results for the COVID-19 pandemic and beyond are discussed.
The implementation of enhanced recovery after surgery pathway in patients undergoing posterior thoracolumbar fusion for degenerative spinal deformity
Authors: Yuan Yi , Wang Shuai-Kang , Chai Xin-Yi , Wang Peng , Li Xiang-Yu , Kong Chao , Lu Shi-Bao
Published: January 2023

Purpose

The prevalence of degenerative spinal deformity (DSD) and the increased cost of correction surgery impose substantial burdens on the health care and insurance system. The aim of our study was to investigate the effects of the implementation of Enhanced Recovery After Surgery (ERAS) protocol on postoperative outcomes after complex spinal surgery.

Methods

A retrospective analysis of prospectively established database of DSD was performed. The consecutive patients who underwent open correction surgery for degenerative spinal deformity between August 2016 and February 2022 were reviewed. We extracted demographic data, preoperative radiographic parameters, and surgery-related variables. The ERAS patients were 1:1 propensity-score matched to a historical cohort by the same surgical team based on age, gender, BMI, and number of levels fused. We then compared the length of hospital stay (LOS), physiological functional recovery, and the rates of complications and readmissions within 90 days after surgery between the groups.

Results

There were 108 patients included, 54 patients in the ERAS cohort, and 54 patients matched control patients in the historical cohort. The historical and ERAS cohorts were not significantly different regarding demographic characteristics, comorbidities, preoperative parameters, operative time, and reoperation rate (P > 0.05). Patients in the ERAS group had significantly shorter postoperative LOS (12.0 days vs. 15.1 days, P = 0.001), average days of drain and urinary catheters placement (3.5 days vs. 4.4 days and 1.9 days vs 4.8 days, respectively), and lower 90-day readmission rate (1.8% vs. 12.9%, P = 0.027). The first day of assisted-walking and bowel movement occurred on average 1.9 days (2.5 days vs. 4.4 days, P = 0.001) and 1.7 days (1.9 days vs. 3.6 days, P = 0.001) earlier respectively in the ERAS group. Moreover, the rate of postoperative urinary retention (3.7% vs. 16.7%, P = 0.026) and surgical site infection (0% vs. 7.4%, P = 0.046) were significantly lower with ERAS protocol applied.

Conclusions

Our study confirmed that the ERAS protocol was safe and essential for patients undergoing thoracolumbar deformity surgery for DSD. The ERAS protocol was associated with a shorter postoperative LOS, a lower rate of 90-day readmission, less rehabilitation discharge, and less postoperative complications.
Network analysis reveals miRNA crosstalk between periodontitis and oral squamous cell carcinoma
Authors: Li Zhengrui , Fu Rao , Wen Xutao , Zhang Ling
Published: January 2023

Background

Oral squamous cell carcinoma (OSCC) is one of the malignant tumors with a poor prognosis. Periodontitis (PD is considered a high-risk factor for OSCC, but the genetic mechanism is rarely studied. This study aims to link OSCC and PD by identifying common differentially expressed miRNAs (Co-DEmiRNAs), their related genes (Hub genes), transcription factors (TFs), signaling pathways, enrichment functions, and compounds, and searching for genetic commonalities.

Methods

The miRNAs expression datasets of OSCC and PD were searched from the GEO database. The miRNA and related crosstalk mechanism between OSCC and PD was obtained through a series of analyses.

Results

hsa-mir-497, hsa-mir-224, hsa-mir-210, hsa-mir-29c, hsa-mir-486-5p, and hsa-mir-31are the top miRNA nodes in Co-DEmiRNA-Target networks. The most significant candidate miRNA dysregulation genes are ZNF460, FBN1, CDK6, BTG2, and CBX6, while the most important dysregulation TF includes HIF1A, TP53, E2F1, MYCN, and JUN. 5-fluorouracil, Ginsenoside, Rh2, and Formaldehyde are the most correlated compounds. Enrichment analysis revealed cancer-related pathways and so on.

Conclusions

The comprehensive analysis reveals the interacting genetic and molecular mechanism between OSCC and PD, linking both and providing a foundation for future basic and clinical research.
Detection and molecular characterization of Clostridium perfringens, Paeniclostridium sordellii and Clostridium septicum from lambs and goat kids with hemorrhagic abomasitis in Turkey
Authors: Kalender Hakan , Öngör Hasan , Timurkaan Necati , Karagülle Burcu , Karabulut Burak , İncili Canan Akdeniz , Başar Hatip Enfal , Ekinci Elif , Çevik Aydın , Atıl Eray , Çetinkaya Burhan
Published: January 2023

Background

The pathogenic Clostridia cause neurotoxic, histotoxic and enterotoxic infections in humans and animals. SeveralClostridiumspecies have been associated with abomasitis in ruminants. The present study aimed to investigate the frequency, and the presence of virulence genes, ofClostridium perfringens, Paeniclostridium sordelliiandClostridium septicumin lambs and goat kids with hemorrhagic abomasitis.

Results

A total of 38 abomasum samples, collected from lambs and goat kids of 1 week to 1 month of age in different farms located in eastern Turkey between 2021 and 2022, were evaluated by histopathology, culture and PCR. At necropsy, the abomasum of the animals was excessively filled with caseinized content and gas, and the abomasum mucosa was hemorrhagic in varying degrees. In histopathological evaluation, acute necrotizing hemorrhagic inflammation was noted in abomasum samples. The examination of swab samples by culture and PCR revealed thatC. perfringenstype A was the most frequently detected species (86.84%) either alone or in combination with otherClostridiumspecies.P. sordellii,C. perfringenstype F andC. septicumwere also harboured in the samples, albeit at low rates. Beta2 toxin gene (cpb2) was found in three ofC. perfringenstype A positive samples.

Conclusion

It was suggested that vaccination of pregnant animals with toxoid vaccines would be beneficial in terms of protecting newborn animals against Clostridial infections. This study investigated the presence of clostridial toxin genes in abomasal samples for the first time in Turkey.
Diagnostic and therapeutic challenges of glioblastoma as an initial malignancy of constitutional mismatch repair deficiency (CMMRD): two case reports and a literature review
Authors: Onishi Shumpei , Yamasaki Fumiyuki , Kuraoka Kazuya , Taguchi Akira , Takayasu Takeshi , Akagi Kiwamu , Hinoi Takao
Published: January 2023

Background

Constitutional mismatch repair deficiency (CMMRD) results from a biallelic germline pathogenic variant in a mismatch repair (MMR) gene. The most common CMMRD-associated malignancies are brain tumors; an accurate diagnosis is challenging when a malignant brain tumor is the only tumor at presentation. We describe two cases of glioblastoma as the initial CMMRD malignancy and discuss current diagnostic and therapeutic challenges.

Case presentation

Two children with brain tumors without remarkable family history had biallelic pathogenic germline variants in PMS2. Patient 1: A 6-year-old girl presented biallelic PMS2 germline pathogenic variants. Glioblastomas at the left frontal lobe and right temporal lobe were resistant to immune-checkpoint inhibitor, temozolomide, and bevacizumab. Patient 2: A 10-year-old boy presented biallelic PMS2 germline variants. His glioblastoma with primitive neuroectodermal tumor-like features responded to chemoradiotherapy, but he developed advanced colon cancer and acute lymphocytic leukemia. In both patients, only a monoallelic PMS2 germline variant was detected by conventional gene tests. PMS2 immunohistochemistry showed lack of staining at both the tumors and normal tissue as vascular endothelial cells. Further gene tests revealed large genomic deletion including the entire PMS2 gene, confirming biallelic PMS2 germline variants.

Conclusion

Conventional multi-gene panel tests are insufficient for detecting large deletions of MMR genes, resulting in misdiagnoses of CMMRD as Lynch syndrome. PMS2 variants have low cancer penetrance; family histories may thus be absent. Long-range gene analyses or immunohistochemical staining of MMR proteins in normal tissue should be considered for pediatric brain tumors with a single allele MMR variant when CMMRD is suspected.
Association of stress hyperglycemia ratio and poor long-term prognosis in patients with myocardial infarction with non-obstructive coronary arteries
Authors: Abdu Fuad A. , Galip Jassur , Qi Penglong , Zhang Wen , Mohammed Abdul-Quddus , Liu Lu , Yin Guoqing , Mohammed Ayman A. , Mareai Redhwan M. , Jiang Rong , Xu Yawei , Che Wenliang
Published: January 2023

Background

Stress hyperglycemia ratio (SHR) is a novel biomarker of true acute hyperglycemia condition and is associated with a worse prognosis in patients with myocardial infarction (MI). However, the effects of SHR in the setting of MI with non-obstructive coronary arteries (MINOCA) have not been investigated. This study aimed to explore the association between SHR and long-term clinical outcomes among MINOCA patients.

Methods

A total of 410 MINOCA patients were included in the final analysis of this study. The patients were divided into three groups based on the SHR tertiles: [SHR1 group (SHR ≤ 0.73), (n = 143); SHR2 group (SHR 0.73–0.84), n = 131; and SHR3 group (SHR ≥ 0.84), n = 136]. Follow-up for major adverse cardiovascular events (MACE) was conducted on all patients. Cox regression and Kaplan–Meier curve analysis were used to evaluate the relationship between SHR and MACE. The receiver operating curve (ROC) analysis was applied to obtain the optimal cut-off value of SHR for predicting clinical MACE.

Results

A total of 92 patients developed MACE during the mean 34 months of follow-up. A significant increase in MACE was observed in the SHR3 group compared to the SHR1 and SHR2 groups (35.3% vs. 15.4% and 16.8%, respectively; P < 0.001). The Kaplan–Meier curves demonstrate that SHR3 patients had the highest MACE risk compared to SHR1 and SHR2 patients (log-rank P < 0.001). In addition, when both SHR tertiles and diabetes status were considered, those with SHR3 and diabetes had the highest hazard of MACE (log-rank P < 0.001). Multivariate Cox regression analysis showed that the SHR3 is associated with a 2.465-fold increase in the risk of MACE (adjusted HR, 2.465; 95% CI 1.461–4.159, P = 0.001). The ROC curve analysis showed that the optimal SHR cut-off value for predicting clinical MACE among MINOCA was 0.86.

Conclusion

Our data indicates, for the first time, that SHR is independently associated with poor long-term prognosis in patients suffering from MINOCA. The optimal SHR cut-off value for predicting clinical MACE among MINOCA patients was 0.86. These findings suggest that SHR may play a potential role in the cardiovascular risk stratification of the MINOCA population.
Metabolic stress constrains microbial L-cysteine production in Escherichia coli by accelerating transposition through mobile genetic elements
Authors: Heieck Kevin , Arnold Nathanael David , Brück Thomas Bartholomäus
Published: January 2023

Background

L-cysteine is an essential chemical building block in the pharmaceutical-, cosmetic-, food and agricultural sector. Conventionally, L-cysteine production relies on the conversion of keratinous biomass mediated by hydrochloric acid. Today, fermentative production based on recombinantE. coli, where L-cysteine production is streamlined and facilitated by synthetic plasmid constructs, is an alternative process at industrial scale. However, metabolic stress and the resulting production escape mechanisms in evolving populations are severely limiting factors during industrial biomanufacturing. We emulate high generation numbers typically reached in industrial fermentation processes withEscherichia coliharbouring L-cysteine production plasmid constructs.So far no genotypic and phenotypic alterations in early and late L-cysteine producingE. colipopulations have been studied.

Results

In a comparative experimental design, theE. coliK12 production strain W3110 and the reduced genome strain MDS42, almost free of insertion sequences, were used as hosts. Data indicates that W3110 populations acquire growth fitness at the expense of L-cysteine productivity within 60 generations, while production in MDS42 populations remains stable. For the first time, the negative impact of predominantly insertion sequence family 3 and 5 transposases on L-cysteine production is reported, by combining differential transcriptome analysis with NGS based deep plasmid sequencing. Furthermore, metabolic clustering of differentially expressed genes supports the hypothesis, that metabolic stress induces rapid propagation of plasmid rearrangements, leading to reduced L-cysteine yields in evolving populations over industrial fermentation time scales.

Conclusion

The results of this study implicate how selective deletion of insertion sequence families could be a new route for improving industrial L-cysteine or even general amino acid production using recombinantE. colihosts. Instead of using minimal genome strains, a selective deletion of certain IS families could offer the benefits of adaptive laboratory evolution (ALE) while maintaining enhanced L-cysteine production stability.
Determinants of ethnic differences in the uptake of child healthcare services in New Zealand: a decomposition analysis
Authors: Lewycka Sonia , Dasgupta Kabir , Plum Alexander , Clark Terryann , Hedges Mary , Pacheco Gail
Published: January 2023

Background

There are persistent ethnic gaps in uptake of child healthcare services in New Zealand (NZ), despite increasing policy to promote equitable access. We examined ethnic differences in the uptake of immunisation and primary healthcare services at different ages and quantified the contribution of relevant explanatory factors, in order to identify potential points of intervention.

Methods

We used data from the Growing Up in New Zealand birth cohort study, including children born between 2009 and 2010. Econometric approaches were used to explore underlying mechanisms behind ethnic differences in service uptake. Multivariable regression was used to adjust for mother, child, household, socioeconomic, mobility, and social factors. Decomposition analysis was used to assess the proportion of each ethnic gap that could be explained, as well as the main drivers behind the explained component. These analyses were repeated for four data time-points.

Results

Six thousand eight hundred twenty-two mothers were enrolled during the antenatal survey, and children were followed up at 9-months, 2-years and 4-years. In univariable models, there were ethnic gaps in uptake of immunisation and primary care services. After adjusting for covariates in multivariable models, compared to NZ Europeans, Asian and Pacific children had higher timeliness and completeness of immunisation at all time-points, while indigenous Māori had lower timeliness of first-year vaccines despite high intentions to immunise. Asian and Pacific mothers were less likely to have their first-choice lead maternity caregiver (LMC) than NZ Europeans mothers, and Māori and Asian mothers were less likely to be satisfied with their general practitioner (GP) at 2-years. Healthcare utilisation was strongly influenced by socio-economic, mobility and social factors including ethnic discrimination. In decomposition models comparing Māori to NZ Europeans, the strongest drivers for timely first-year immunisations and GP satisfaction (2-years) were household composition and household income. Gaps between Pacific and NZ Europeans in timely first-year immunisations and choice of maternity carer were largely unexplained by factors included in the models.

Conclusions

Ethnic gaps in uptake of child healthcare services vary by ethnicity, service, and time-point, and are driven by different factors. Addressing healthcare disparities will require interventions tailored to specific ethnic groups, as well as addressing underlying social determinants and structural racism. Gaps that remain unexplained by our models require further investigation.
Predictive significance of surgery-induced lymphopenia on the survival after curative resection for locally advanced gastric cancer: a retrospective cohort analysis
Authors: Aizawa Masaki , Yabusaki Hiroshi , Matsuki Atsushi , Bamba Takeo , Nakagawa Satoru
Published: January 2023

Background

Following the establishment of the anti-cancer effect of immune checkpoint inhibitors, lymphopenia has attracted attention as a parameter of preexisting cancer-related immune tolerance. Although the pretreatment absolute lymphocyte count (ALC) has been reported as a prognostic factor in gastric cancer patients, the impact of perioperative changes in the ALC remains unknown. The aim of the present study was to explore the relationship between surgery-induced lymphopenia and outcome.

Methods

Database entries for 584 patients who underwent curative resections for pathological Stage IB-III gastric cancer were reviewed. We retrospectively compared clinicopathological factors including pretreatment ALC (pre-ALC) and ALC at first visit after discharge (post-ALC) with the survival. The low ALC was defined as < 1000/μL.

Results

The ALC decreased significantly at 1 and 3 days after surgery and then recovered to the baseline value. A low pre-ALC (p < 0.001) and a low post-ALC (p < 0.001) were both correlated with a poor relapse-free survival (RFS). A multivariate analysis of RFS identified a low post-ALC (hazard ratio 1.875, 95% CI 1.156–3.402, p = 0.01), age, gender, BMI, T disease, N disease, severe vessel invasion, type of gastrectomy and postoperative morbidity as independent factors. The low post-ALC group had a poor RFS among patients with Stage II (p = 0.04) and Stage III (p = 0.04) disease, but not among patients with Stage IB disease (p = 0.13). Consistently, the overall survival (OS) rate was significantly lower among patients with a low post-ALC for all stage (p < 0.001), stage II (p = 0.02) and stage III (p = 0.01) disease, not for stage IB (p = 0.09). A low post-ALC was identified as an independent factor for predicting OS by multivariate analysis (hazard ratio: 2.275, 95% CI 1.373–3.769, p = 0.01).

Conclusions

A decrease in post-ALC was correlated with both of RFS and OS after curative resection in patients with locally advanced gastric cancer.

Highlights

Postoperative lymphopenia was a poor prognostic factor for gastric cancer.
Effects of dynamic body weight support on functional independence measures in acute ischemic stroke: a retrospective cohort study
Authors: Huber Justin , Elwert Nicholas , Powell Elizabeth Salmon , Westgate Philip M. , Hines Emily , Sawaki Lumy
Published: January 2023

Background

Stroke remains a major public health concern in the United States and a leading cause of long-term disability in adults. Dynamic body weight support (DBWS) systems are popular technology available for use in clinical settings such inpatient rehabilitation. However, there remains limited studies in such inpatient settings that compare DBWS to standard of care (SOC) using real world outcome measures. For survivors of acute ischemic stroke, we determine if incorporating a dynamic body weight support (DBWS) system into inpatient therapy offers greater improvement than standard of care (SOC).

Methods

A retrospective chart review included 52 individuals with an acute ischemic stroke admitted to an inpatient rehabilitation facility. Functional Independence Measure (FIM) data, specifically changes in FIM at discharge, served as the primary outcome measure. Patient cohorts received either therapies per SOC or therapies incorporating DBWS. Regardless of cohort group, all patients underwent therapies for 3 h per day for 5 days a week.

Results

For both groups, a statistically and clinically significant increase in total FIM (P < 0.0001) was observed at discharge compared to at admission. Improvements for the DBWS group were significantly greater than the SOC group as evidenced by higher gains in total FIM (p = 0.04) and this corresponded to a medium effect size (Cohen’s d = 0.58). Among FIM subscores, the DBWS group achieved a significant increase in sphincter control while all other subscore changes remained non-significant.

Conclusions

This preliminary evidence supports the benefit of using DBWS during inpatient rehabilitation in individuals who have experienced an acute ischemic stroke. This may be due to the greater intensity and repetitions of tasks allowed by DBWS. These preliminary findings warrant further investigations on the use of DBWS in inpatient settings.
Perivascular epithelioid cell tumor of the uterine cervix identified on the liquid-based cytology: a case report
Authors: Tang Xiao , Feng Min , Shen Yangmei , Chen Qijun
Published: January 2023

Background

Perivascular epithelioid cell tumor (PEComa) occurring in the female genital tract are rare, and typically found in the uterine corpus. PEComa occurring in the cervix is extremely rare, and very few cases have been reported till now. Cytological diagnosis of cervical PEComa is even rarer. So far, only two cases of PEComa diagnosed by conventional cervical smears have been reported.

Case presentation

A 55-year-old postmenopausal woman presented with abnormal vagina discharge for 3 months. A liquid-based cytology test was performed. Microscopically, some loosely cohesive epithelioid cells were uniform with abundant clear cytoplasm, showing predominantly round or oval nuclei with finely stippled chromatin. Distinct round nucleoli were visible in some cells, notably with numerous melanin pigments in the cytoplasm. The cytopathological features were well correlated with cell block and histopathological findings. Upon immunohistochemistry (IHC), the tumor cells were positive for HMB45 and TFE3, focally positive for MelanA, while negative for muscle marker. Fluorescence in situ hybridization (FISH) confirmed TFE3 gene rearrangement. The final pathological diagnosis was PEComa identified by the liquid-based cytology, cell block, cervical biopsy, IHC and FISH result. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy and was followed up for 2 years with no evidence of disease.

Conclusion

The cytologic characteristics of the tumor can provide sufficient clues for PEComa diagnosis, which includes loosely cohesive, epithelioid morphology with abundant clear or eosinophilic cytoplasm, low-grade nuclear atypia, cytoplasmic melanin pigments. This will help cytopathologists to recognize this rare tumor that occurred in the cervix, and the combination of predictive morphology evaluation, immunophenotype, and molecular testing can achieve the definitive diagnosis of PEComa.
Association between total cholesterol and total bone mineral density in US adults: National Health and Nutrition Examination Survey (NHANES), 2011–2018
Authors: cao Li , Wu Wei , Deng Xiangyu , Guo Haoyu , Pu Feifei , Shao Zengwu
Published: January 2023

Background

Accumulated evidence indicates that cholesterol is offensive to bone metabolism. Therefore, we examined the real-world study among total cholesterol and total bone mineral density (BMD). We investigated the relationship between total cholesterol and total BMD among 10,039 US participants aged 20–59 years old over the period 2011–2018 from the NHANES.

Methods

To analyze the relationship among total cholesterol and total BMD, multivariate linear regression models were used. Fitted smoothing curves, generalized additive models, and threshold effect analysis were also conducted.

Results

After adjusting for additional covariates, weighted multivariable linear regression models indicated total cholesterol concentration levels exhibited a negative relationship with total BMD, particularly among participants aged 20–29 years. Concerning subgroup analysis, stratified by gender, race/ethnicity and age group, the negative correlation of total cholesterol with total BMD dwelled in both female and male as well as in whites and other races (including Hispanic and Multi-Racial), but not in non-Hispanic blacks and Mexican American. In other races, this relationship presented a nonlinear association (inflection point: 6.7 mmol/L) with a U-shaped curve. Among participants aged 40 to 49 years, this relationship also followed a nonlinear association (inflection point: 5.84 mmol/L), indicating a saturation effect. Moreover, the three types of diabetes status were found to have negative, U-shaped, and positive relationships. In participants with borderline diabetes status, the relationship of total cholesterol with total BMD was a U-shaped curve (inflection point: 4.65 mmol/L).

Conclusions

For US young adults (20–29 years old), our study revealed a negative relationship between total cholesterol and total BMD. This association followed a U-shaped curve (inflection point: 4.65 mmol/L) in borderline diabetes status participants, a saturation curve (inflection point: 5.84 mmol/L) in participants aged 40–49 years and a nonlinear curve (inflection point: 6.7 mmol/L) in other races (including Hispanic and Multi-Racial). Therefore, keeping total cholesterol concentration at a reasonable level for young adults and diabetic population might be an approach to prevent osteoporosis or osteopenia.