bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and factors associated with underweight among 15–49-year-old women in Sierra Leone: a secondary data analysis of Sierra Leone demographic health survey of 2019
Authors: Ikoona Eric Nzirakaindi , Toure Mame Awa , Njenga Amon , Namulemo Lucy , Kaluya Ronald , Kamara Kassim , Oyat Freddy Wathum Drinkwater , Aloyo Judith , Kitara David Lagoro
Published: April 2023

Background

Women are at higher risks of being underweight than men due to biological, socio-economic, and cultural factors. Underweight women have high risks of poor obstetric outcomes. We aimed to determine the prevalence and factors associated with being underweight among women of reproductive age (15–49 years) in Sierra Leone.

Methods

We used Sierra Leone Demographic and Health Survey (2019-SLDHS) data of 7,514 women aged 15 to 49 years, excluding pregnant, post-natal, lactating, and post-menopausal women. A multistage stratified sampling approach was used to select study participants, and data was collected using validated questionnaires. A multivariable logistic regression analysis was used to determine factors associated with underweight among 15–49-year-old women in Sierra Leone. Ethical approval for the study was obtained.

Results

The prevalence of underweight was 6.7% (502/7,514). Underweight was likely among age-group of 15–24 years, AOR = 2.50,95%CI:2.39–2.60;p < 0.001 compared to 25–34 year age-group and likely among women with parity of one to four, AOR = 1.48,95%CI:1.08–2.03;p = 0.015 compared to women who never gave birth. Underweight was unlikely among women who did not listen to radios AOR = 0.67,95%CI:0.55–0.83;p < 0.001 compared to those who did; women from the north AOR = 0.73,95%CI:0.56–0.96;p = 0.026 compared to the east, and not married women AOR = 0.59,95%CI:0.47–0.76;p < 0.001 compared to married. All household wealth indices were not significantly associated with underweight.

Conclusion

The prevalence of underweight among women in the reproductive age (15–49 years) in Sierra Leone was 6.7% and it is lower compared to global and most sub-Saharan African data. Factors associated with underweight were 15–24-year age-group, and parity of one to four. Being underweight was unlikely among women who did not listen to radios, women from the north and not married. All household wealth indices were not significantly associated with underweight. Even though household wealth indices were not significantly associated with being underweight, most underweight women 68.7% (345/502) were in the poorest, poorer, and middle household wealth indices. The need to address socio-economic determinants of underweight among women (aged 15–49 years) due to household poverty is a priority in Sierra Leone.
Beliefs around the causes of inequities and intergroup attitudes among health professional students before and after a course related to Indigenous Peoples and colonialism
Authors: Melro Carolyn M. , Matheson Kimberly , Bombay Amy
Published: April 2023

Background

Addressing the Truth and Reconciliation Calls to Action on including anti-racism and cultural competency education is acknowledged within many health professional programs. However, little is known about the effects of a course related to Indigenous Peoples and colonialism on learners’ beliefs about the causes of inequities and intergroup attitudes.

Methods

A total of 335 learners across three course cohorts (in 2019, 2020, 2022) of health professional programs (e.g., Dentistry/Dental Hygiene, Medicine, Nursing, and Pharmacy) at a Canadian university completed a survey prior to and 3 months following an educational intervention. The survey assessed gender, age, cultural identity, political ideology, and health professional program along with learners’ causal beliefs, blaming attitudes, support for social action and perceived professional responsibility to address inequities. Pre-post changes were assessed using mixed measures (Cohort x Time of measurement) analyses of variance, and demographic predictors of change were determined using multiple regression analyses. Pearson correlations were conducted to assess the relationship between the main outcome variables.

Results

Only one cohort of learners reported change following the intervention, indicating greater awareness of the effects of historical aspects of colonialism on Indigenous Peoples inequities, but unexpectedly, expressed stronger blaming attitudes and less support for government social action and policy at the end of the course. When controlling for demographic variables, the strongest predictors of blaming attitudes towards Indigenous Peoples and lower support for government action were gender and health professional program. There was a negative correlation between historical factors and blaming attitudes suggesting that learners who were less willing to recognize the role of historical factors on health inequities were more likely to express blaming attitudes. Further, stronger support for government action or policies to address such inequities was associated with greater recognition of the causal effects of historical factors, and learners were less likely to express blaming attitudes.

Conclusion

The findings with respect to blaming attitudes and lower support for government social action and policies suggested that educational interventions can have unexpected negative effects. As such, implementation of content to address the Truth and Reconciliation Commissions Calls to Action should be accompanied by rigorous research and evaluation that explore how attitudes are transformed across the health professional education journey to monitor intended and unintended effects.
Utilisation of rural primary health centers for outpatient services - a study based on Rajasthan, India
Authors: Srivastava Ambey Kumar , Gupt Rajan Kumar , Bhargava Ruchi , Singh Rajesh Ranjan , Songara Dinesh
Published: April 2023

Introduction

Outpatient services are crucial for strengthening primary healthcare and reducing out-of-pocket spending, which has been one of the major causes of impoverishment. So it is also critical to comprehend the people’s preferences in accessing primary healthcare facilities, as government primary healthcare facilities in India are underutilized. The current paper explores the factors that construct the individual’s decision to seek outpatient care in primary healthcare facilities in India’s largest state Rajasthan.

Methods

It was a cross-sectional survey conducted in 72 primary sample units of 24 primary health centers in 11 districts of Rajasthan, India, from November 2019 to January 2020. The study selected 368 households through purposive sampling. Out of 368 households, 460 people reported any illness and 326 reported outpatient visit to any health facility in the last 30 days from the date of the survey.

Analysis

The focus was on analyzing the data in the context of public and private health facilities to understand the factors influencing people’s choice to access outpatient services. The principal component analysis is used to understand the relationship between facility preparedness and OPD uptake. Also, multivariate logistic regression is applied to assess the significant predictors in using primary health facility services.

Result

Except for the 29% of patients who received no care, the proportion of patients attended public health facilities was 35%, and the rest were utilizing private health facilities. Those who sought care at PHCs were mostly over 45 years age, non-literate, and from the lowest wealth quintile. Logistic regression suggests that people belong to upper wealth quintile (OR = 0.298; 95% 0.118–0.753) are less likely to visit PHCs for treatment. Also, increase in distance of PHC (OR = 0.203; 95% CI 0.076–0.539) reduces the likelihood of their visit outpatient care. People are 9.7 times (OR = 9.740; 95% CI 2.856–33.217) more likely to visit a PHCs that are better equipped in terms of human resources, equipment, and medicine.

Conclusion

The uptake of PHCs depends on several factors, which should be considered to ensure that all segments of society have equitable access to them. Through improved accessibility and quality of service, PHCs can be made more appealing to the larger population.
Slack resources and individual performance of clinicians: the mediating role of job satisfaction and empirical evidence from public hospitals in Beijing, China
Authors: Lu Wei , Song Xinrui , Zhu Junli , Zhang Yao , Hou Changmin
Published: April 2023

Background

Clinicians in Chinese public hospitals face a complex and severe clinical practice environment, and the individual performance of clinicians is key to improving the output of the healthcare industry. This study aims to explore the mechanism of slack resources in improving individual performance of clinicians and the role of job satisfaction in this process, while the study framework is based on the widely applied Job-Demands Resources theory.

Methods

Based on the study framework composed of slack resources, individual performance, and job satisfaction, hypotheses have been put forward, and questionnaires have been distributed to representative clinicians in tertiary public hospitals. Finally, 318 valid data collected from clinicians have been obtained. To verify the hypotheses, multiple linear regression models have been established to explore the relationship between variables, and the three-stage regression models have been used to verify the presence of mediating role.

Results

All four hypotheses proposed in this study have been proved to be held. Clinicians' job satisfaction has played a mediating role in the impact of slack resources and its three dimensions on individual performance. Among them, there has been a complete mediating role for staff slack, while time and space dimensions have played a partial mediating role in the impact of slack resources on individual performance.

Conclusions

In public hospitals in environments where behavior is subject to significant government interference, it is necessary and feasible to retain appropriate slack resources to improve individual performance. From the perspective of resources management in hospitals, it is necessary for public hospitals to implement a strategy of reserving an appropriate portion of time, staff and space in order to have the conditions to improve clinicians' satisfaction. The existence of slack resources in public hospitals can improve the job satisfaction of clinicians, and then improve the individual performance through the process.
Explanations for variations in hospital expenditures among four large California counties
Authors: Lansdale Aimee J. , Kaplan Robert M.
Published: April 2023

Objective

To investigate competing explanations for why Medicare Fee for Service (FFS) and private sector payments lead to hospital cost variations in Californian counties.

Data sources

Ratios of private to Medicare hospital costs were obtained from state-based all-payer claims databases. Demographics were estimated from the U.S. Census Bureau and the California Health Interview Survey. Medicaid and Medicare spending was obtained from Kaiser Family Foundation. Medicare Advantage enrollment was obtained from the California Department of Health Care Services and market consolidation was estimated using the Herfindahl–Hirschman Index (HHI).

Study design

Per capita costs, demographics, Medicaid and Medicare spending, Medicare Advantage enrollment, and HHI scores were compared for San Francisco (SF), Sacramento, Los Angeles (LA), and San Diego (SD).

Principal findings

LA hospitals had the lowest per capita private insurer costs, but the highest Medicare FFS costs. The findings might be explained by a lower HHI for LA, indicating a more competitive market, than SD, SF, and Sacramento.

Conclusions

Medicare FFS hospital costs do not provide an accurate representation of health care spending in Californian counties. In more competitive markets, private insurance companies can negotiate lower prices, while oversupply may allow facilities to increase volume in Medicare FFS.
PCR-confirmed malaria among children presenting with a decreased level of consciousness in Angola: a prospective, observational study
Authors: Savonius Okko , de Souza Cintia F. , Fançony Cláudia , Cruzeiro Manuel Leite , Brito Miguel , Pelkonen Tuula
Published: April 2023

Background

In malaria-endemic areas, children presenting to hospitals with a decreased level of consciousness remain a diagnostic dilemma. The definition of cerebral malaria in a comatose child demands exclusion of other possible reasons, which requires in-depth investigations that are not easily available. The aim of this study was to investigate the frequency and clinical characteristics of PCR-confirmed malaria in a cohort of children with a decreased level of consciousness, look for potential features that would aid in differentiating children with malaria from those without, and assess the performance of traditional thick film microscopy against the cytb-qPCR-method.

Methods

A total of 345 children aged 30 days–15 years old, presenting to Hospital Pediátrico David Bernardino in Luanda, Angola, with a decreased level of consciousness (Glasgow coma scale score < 15) were prospectively enrolled during 2014–2017. Malaria was defined as a positive cytb-qPCR result on any occasion in hospital. The clinical course and laboratory parameters were compared between children with malaria and those without. The performance of thick film microscopy was analysed against the PCR method.

Results

161 of 345 children (46.7%) had a positive malaria PCR test result. All cases were Plasmodium falciparum species, and 82.6% (133/161) fulfilled the WHO criteria for severe malaria. Overall, children with malaria presented to hospital with a shorter duration of symptoms and less convulsions pre-admission compared to those without malaria. The median GCS score on admission was 8, which did not differ between children with or without malaria. Clinical findings on admission were mostly similar across the whole cohort, but an infection focus outside the central nervous system was more common in malaria-negative children. Moreover, severe anaemia, thrombocytopenia, and high CRP levels occurred more frequently in children with malaria. The case fatality ratio was 28.5% (91/319) and did not differ between parasitaemic children and those without malaria, although parasitaemic children died sooner after hospital admission. When neurological sequelae were also considered, a positive malaria test was associated with a better outcome. The performance of thick film microscopy against PCR yielded a sensitivity of 96.8% and a specificity of 82.7%.

Conclusions

In this cohort of children with a decreased consciousness, the frequent presence of a malarial infection could not be judged from the clinical findings on admission, but the combination of profound aneamia, thrombocytopenia, and a high CRP level increased the odds of a positive malaria test result. Mortality remained high regardless of etiology, but malaria infection associated with fewer neurological deficits at discharge. Thick film microscopy performed well compared to the cytb-qPCR method.
Junior surgeons are quicker to master the single-port thoracoscopic lobectomy: comprehensive analysis of the learning curve and oncological outcomes
Authors: Liang Mingqiang , Wu Peixun , Xu Chi , Zheng Bin , Chen Chun
Published: April 2023

Background

The learning curve of single-port thoracoscopic lobectomy (SPTL) in lung cancer has been widely studied. However, the efficiency of different experience levels of thoracic surgeons in mastering the learning curve is unknown. Hence, we discuss this issue in depth by using several perioperative parameters and oncological outcomes.

Methods

A total of 120 consecutive cases of SPTL performed by a senior (STS group) and junior (JTS group) thoracic surgeons were retrospectively analyzed. Operation time, estimated blood loss, and duration of postoperative hospital stay were recorded for cumulative summation (CUSUM) learning curve analysis, while the 5-year survival rate was used for oncological evaluation.

Results

The CUSUM learning curve of the STS group was y = 0.000106x3 − 0.019x2 + 0.852x − 0.036, with a high R-value of 0.9517. When the number of cases exceeded 33, the slope changed from positive to negative. The CUSUM learning curve of the JTS group was y = 0.000266x3 − 0.04x2 + 1.429 × –0.335, with a high R-value of 0.9644. When the number of cases exceeded 25, the slope changed from positive to negative. The learning curve was divided into two phases (phases 1 and 2). The slope of the JTS group in phase 1 was greater than that of the STS group in phase 1 (p < 0.001). Meanwhile, comparisons of various parameters between both groups in phase 2 showed no statistically significant difference (p > 0.05). In addition, the 5-year survival rate was not significantly different between the two groups (p = 0.72).

Conclusion

This is the first study to analyze the learning curve of thoracic surgeons with different experience levels in mastering SPTL. Moreover, it is also the first study to include multiple perioperative parameters and overall survival to study how quickly surgeons master the SPTL technique. The junior thoracic surgeon was found to have a shorter learning curve for SPTL.
Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type I interferonopathies (NNS/CANDLE, SAVI, And AGS)
Authors: Kanazawa Nobuo , Ishii Taeko , Takita Yasushi , Nishikawa Atsushi , Nishikomori Ryuta
Published: April 2023

Background

This study evaluated the efficacy and safety of baricitinib (Janus kinase-1/2 inhibitor), in adult and pediatric Japanese patients with Nakajo-Nishimura syndrome/chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (NNS/CANDLE), stimulator of interferon genes-associated vasculopathy with onset during infancy (SAVI), or Aicardi-Goutières syndrome (AGS).

Methods

A Phase 2/3, multicenter, open-label study (NCT04517253) was conducted across 52 weeks. Primary efficacy endpoint assessed the change in mean daily diary score (DDS) from baseline to the end of primary treatment period. Other efficacy endpoints included change in mean DDS to the end of maintenance period, daily corticosteroid use, Physician’s Global Assessment of Disease Activity (PGA) scores, and daily symptom-specific score (DSSS) from baseline to primary and maintenance treatment periods. All treatment-emergent adverse events (TEAEs) that occurred postdosing were recorded.

Results

Overall, 9 patients (5 with NNS, 3 with SAVI, and 1 with AGS) were enrolled; 55.6% were females, mean age was 26 years, and mean corticosteroid use/weight was 0.2 mg/kg. At the end of primary treatment period, mean DDS decreased from baseline in patients with NNS/CANDLE (0.22) and SAVI (0.21) and increased in the patient with AGS (0.07). At the end of maintenance treatment period, mean DDS decreased from baseline in patients with NNS/CANDLE (0.18) and SAVI (0.27) and increased in the patient with AGS (0.04). Mean percent corticosteroid use decreased by 18.4% in 3 out of 5 patients with NNS/CANDLE and 62.9% in 1 out of 3 patients with SAVI. Mean PGA score decreased from baseline in patients with NNS/CANDLE (1.60), SAVI (1.33), and AGS (1.0), and mean DSSS improved from baseline. All patients reported ≥ 1 TEAE. Frequently reported AEs included BK polyomavirus detection (3; 33.3%), increased blood creatine phosphokinase (2; 22.2%), anemia (2; 22.2%), and upper respiratory tract infection (2; 22.2%). Three (33.3%) patients reported serious adverse events, 1 of which was related to study drug. One patient with SAVI died due to intracranial hemorrhage, which was not related to study drug.

Conclusion

Baricitinib may offer a potential therapeutic option for patients with NNS/CANDLE, SAVI, and AGS, with a positive benefit/risk profile in a vulnerable patient population with multiple comorbidities.

Trial registration

NLM clinicaltrials.gov, NCT04517253. Registered 18 August 2020.
Development of an endoplasmic reticulum stress-related signature with potential implications in prognosis and immunotherapy in head and neck squamous cell carcinoma
Authors: Fan Xinlong , Yang Xiao , Guo Nan , Gao Xin , Zhao Yuejiao
Published: April 2023

Background

Head and neck squamous cell carcinoma (HNSCC) is a multisite malignancy that responds well to immunotherapy. Despite the initial enthusiasm, the clinical benefits of immunotherapy in HNSCC patients are overall limited. Endoplasmic reticulum stress (ERS) has been indicated to play a key role in the process of anti-tumor immune response mediation. However, ERS-related biomarkers which can accurately predict prognosis and immunotherapy response in HNSCC are still lacking.

Methods and results

In this study, we identify and validate an ERS-related signature comprises of six genes (ASNS, EXOSC6, BAK1, TPP1, EXOSC8, and TATDN2) that can predict the prognosis of HNSCC patients. GSEA analysis indicates that the ERS-related signature is significantly correlated with tumor immunity in HNSCC. Moreover, the infiltration of naive B cells and CD8 + T cells are significantly diminished in patients with high-risk scores compared to those with low-risk scores, while macrophages and activated mast cells are remarkably enhanced. Furthermore, the ERS-related signature also displays a tremendous potential for predicting immunotherapy response in HNSCC.

Conclusions

Our study identifies an ERS-related signature that can predict the prognosis of HNSCC patients and highlights its potential value as a predictive biomarker of immunotherapy response, potentially enabling more precise and personalized immunotherapy response and paving the way for further investigation of the prognostic and therapeutic potentials of ERS.
Sweden’s first Take-Home Naloxone program: participant characteristics, dose endpoints and predictors for overdose reversals
Authors: Holmén Elin , Warnqvist Anna , Kåberg Martin
Published: April 2023

Background

Opioid overdoses are a growing concern, particularly among people who inject drugs. Sweden, with a comparatively high proportion of drug-related mortality, introduced its first Take-Home Naloxone (THN) program in 2018, at the Stockholm needle and syringe program (NSP). In this study we compare THN participant characteristics regarding refills and overdose reversals as well as investigate predictors associated with number of reversals. We also investigate interventions performed in overdose situations and endpoints for naloxone doses.

Methods

This was a prospective open inclusion cohort study conducted between January 24th 2018 and March 31st 2022 at the Stockholm NSP. Participants received THN, free of charge, after a training session and provided data regarding drug use and overdose experiences. During refill visits, participants reported if the naloxone was used for overdose reversal and, if so, responded to a ten-item questionnaire which included stating whether the naloxone recipient was the participant themselves or somebody else. Questionnaire data was combined with NSP database demographic data. Zero-inflated Poisson regression was applied to analyse predictors for number of reported overdose reversals.

Results

Among study participants (n = 1,295), 66.5% stated opioids as their primary drug, and 61.4% and 81.0% had previous experience of a personal or witnessed overdose, respectively. Overall, 44.0% of participants reported a total of 1,625 overdose reversals and the victim was known to have survived in 95.6% of cases. Stimulant use (aIRR 1.26; 95% CI 1.01, 1.58), benzodiazepine use (aIRR 1.75; 95% CI 1.1, 2.78) and homelessness (aIRR 1.35; 95% CI 1.06, 1.73) were predictors associated with an increased number of reported overdose reversals. Mortality was higher among those who reported at least one overdose reversal (HR 3.4; 95% CI 2.2, 5.2).

Conclusions

An NSP’s existent framework can be utilised to effectively implement a THN program, provide basic training and reach numerous high-risk individuals. During the four-year study, THN participants reversed a sizeable number of potentially fatal overdoses, of which many were reported by participants whose primary drug was not opioids. Naloxone refill rate was high, indicating that participants were motivated to maintain a supply of naloxone in case of future overdose events.
FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling
Authors: Yang Yiqi , Zhang Yibo , Cao Jieqiong , Su Zijian , Li Fu , Zhang Peiguang , Zhang Bihui , Liu Rongzhan , Zhang Linhao , Xie Junye , Li Jingsheng , Zhang Jinting , Chen Xiaojia , Hong An
Published: April 2023

Background

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide, but current treatment options remain limited and cause serious life-threatening side effects. Aberrant FGFR4 signaling has been validated as an oncogenic driver of HCC, and EZH2, the catalytic subunit of the PRC2 complex, is a potential factor that contributes to acquired drug resistance in many tumors, including HCC. However, the functional relationship between these two carcinogenic factors, especially their significance for HCC treatment, remains unclear. In this study, we systematically evaluated the feasibility of a combination therapy targeting FGFR4 and EZH2 for HCC.

Methods

RNA sequencing data of patients with Liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) were analyzed to determine FGFR4 and EZH2 expression and their interaction with prognosis. Moreover, the HCC cell lines, zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors were treated with FGFR4 inhibitor (Roblitinib) and/or EZH2 inhibitor (CPI-169) and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for HCC both in vitro and in vivo. Furthermore, RNA-Seq was performed in combination with ChIP-Seq data analysis to investigate the critical mechanism underlying the combination treatment with Roblitinib and CPI-169.

Results

EZH2 accumulated through the non-canonical NF-kB signaling in response to FGFR4 inhibitor treatment, and the elevated EZH2 levels led to the antagonism of HCC against Roblitinib (FGFR4 inhibitor). Notably, knockdown of EZH2 sensitized HCC cells to Roblitinib, while the combination treatment of Roblitinib and CPI-169 (EZH2 inhibitor) synergistically induced the HCC cell apoptosis in vitro and suppressed the zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors development in vivo. Moreover, Roblitinib and CPI-169 synergistically inhibited HCC development via repressing YAP signaling.

Conclusions

Collectively, our study highlighted the potential of the therapeutic combination of FGFR4 and EZH2 inhibitors, which would provide new references for the further development of clinical treatment strategies for HCC.
Knockdown of heat shock protein family D member 1 (HSPD1) promotes proliferation and migration of ovarian cancer cells via disrupting the stability of mitochondrial 3-oxoacyl-ACP synthase (OXSM)
Authors: Duan Yaoyun , Yu Juan , Chen Miaojuan , Lu Qinsheng , Ning Fen , Gan Xiaowen , Liu Hanbo , Ye Yixin , Lu Shenjiao , Lash Gendie E.
Published: April 2023

Background

Heat shock protein 60 (HSP60) is essential for the folding and assembly of newly imported proteins to the mitochondria. HSP60 is overexpressed in most types of cancer, but its association with ovarian cancer is still in dispute. SKOV3 and OVCAR3 were used as experimental models after comparing the expression level of mitochondrial HSP60 in a normal human ovarian epithelial cell line and four ovarian cancer cell lines.

Results

Low HSPD1 (Heat Shock Protein Family D (HSP60) Member 1) expression was associated with unfavorable prognosis in ovarian cancer patients. Knockdown of HSPD1 significantly promoted the proliferation and migration of ovarian cancer cells. The differentially expressed proteins after HSPD1 knockdown were enriched in the lipoic acid (LA) biosynthesis and metabolism pathway, in which mitochondrial 3-oxoacyl-ACP synthase (OXSM) was the most downregulated protein and responsible for lipoic acid synthesis. HSP60 interacted with OXSM and overexpression of OXSM or LA treatment could reverse proliferation promotion mediated by HSPD1 knockdown.

Conclusions

HSP60 interacted with OXSM and maintained its stability. Knockdown of HSPD1 could promote the proliferation and migration of SKOV3 and OVCAR3 via lowering the protein level of OXSM and LA synthesis.
Treatment for ovarian clear cell carcinoma with combined inhibition of WEE1 and ATR
Authors: Chien Wenwen , Tyner Jeffrey W. , Gery Sigal , Zheng Yueyuan , Li Li-Yan , Gopinatha Pillai Mohan Shankar , Nam Chehyun , Bhowmick Neil A. , Lin De-Chen , Koeffler H. Phillip
Published: April 2023

Background

Standard platinum-based therapy for ovarian cancer is inefficient against ovarian clear cell carcinoma (OCCC). OCCC is a distinct subtype of epithelial ovarian cancer. OCCC constitutes 25% of ovarian cancers in East Asia (Japan, Korea, China, Singapore) and 6–10% in Europe and North America. The cancer is characterized by frequent inactivation of ARID1A and 10% of cases of endometriosis progression to OCCC. The aim of this study was to identify drugs that are either FDA-approved or in clinical trials for the treatment of OCCC.

Results

High throughput screening of 166 compounds that are either FDA-approved, in clinical trials or are in pre-clinical studies identified several cytotoxic compounds against OCCC. ARID1A knockdown cells were more sensitive to inhibitors of either mTOR (PP242), dual mTOR/PI3K (GDC0941), ATR (AZD6738) or MDM2 (RG7388) compared to control cells. Also, compounds targeting BH3 domain (AZD4320) and SRC (AZD0530) displayed preferential cytotoxicity against ARID1A mutant cell lines. In addition, WEE1 inhibitor (AZD1775) showed broad cytotoxicity toward OCCC cell lines, irrespective of ARID1A status.

Conclusions

In a selection of 166 compounds we showed that inhibitors of ATR and WEE1 were cytotoxic against a panel of OCCC cell lines. These two drugs are already in other clinical trials, making them ideal candidates for treatment of OCCC.
Hypertonic sodium lactate infusion reduces vasopressor requirements and biomarkers of brain and cardiac injury after experimental cardiac arrest
Authors: Annoni Filippo , Su Fuhong , Peluso Lorenzo , Lisi Ilaria , Caruso Enrico , Pischiutta Francesca , Gouvea Bogossian Elisa , Garcia Bruno , Njimi Hassane , Vincent Jean-Louis , Gaspard Nicolas , Ferlini Lorenzo , Creteur Jacques , Zanier Elisa R. , Taccone Fabio Silvio
Published: April 2023

Introduction

Prognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA.

Methods

After a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C.

Results

Thirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p < 0.001), whereas potassium concentrations were lower (p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls.

Conclusions

In this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury.
Smell and taste of milk during tube feeding of preterm infants: neurodevelopmental follow-up of the randomized TASTE trial, study protocol
Authors: Beker Friederike , Hughes Ian P. , Jacobs Sue , Liley Helen G. , Bora Samudragupta , Simcock Gabrielle , Davis Peter G.
Published: April 2023

Background

The Taste And Smell To Enhance nutrition (TASTE) trial investigated the effects of smell and taste of milk with tube feeding compared to routine care on the growth of preterm infants. There was no difference between groups in growth (weight, head circumference, length) z-scores at discharge from the hospital. Infants in the intervention group had higher head circumference and length z-scores at 36 weeks postmenstrual age, both secondary outcomes. The objective of this follow-up study is to assess 2-year neurodevelopmental and growth outcomes after exposure of preterm infants to the smell and taste of milk with tube feeding compared to routine care.

Methods

This is a neurodevelopmental follow-up study of a two-center, placebo-controlled randomized trial. Infants born before 29 weeks postmenstrual age and/or with a birth weight of less than 1250 g were randomized to smell and taste of milk with each tube feed or routine care. The current follow-up assessed the 2-year neurodevelopmental and growth outcomes of participants of the TASTE trial discharged from the hospital (n = 334). The primary outcome is survival free of any major neurodevelopmental impairment comprising any moderate/severe cerebral palsy (Gross Motor Function Classification System score II–V), Bayley Scales of Infant and Toddler Development, Third/Fourth Edition (Bayley-III/Bayley-4) motor, cognitive, or language scores < -2SD, blindness, or deafness at 2 years of age. Other outcomes include death, breastfeeding within the first year, and respiratory support, oral feeding, and anthropometric parameters at 2 years of age. The Human Research Ethics Committees of Mater Misericordiae Limited and the Royal Women’s Hospital approved the TASTE trial including the neurodevelopmental follow-up described in this protocol.

Discussion

For patients and their families, the neurodevelopmental outcomes of preterm infants are of utmost importance. Consequently, they should be investigated following any interventional study performed during the newborn period. Furthermore, improved weight gain and head growth in the hospital are associated with better long-term neurodevelopmental outcomes. Smelling and tasting of milk is an uncomplicated and cost-effective intervention that may improve the growth and neurodevelopmental outcomes of preterm infants. Potential limitations affecting this follow-up study, caused by the COVID-19 pandemic, are anticipated and discussed in this protocol.

Trial registration

Name of the registry: Australian and New Zealand Clinical Trials Registry; Registration number: ACTRN12617000583347; Registration date: 26 April 2017.
A novel spectrophotometric approach relies on a charge transfer complex between atomoxetine with quinone-based π-acceptor. Application to content uniformity test
Authors: Abu-hassan Ahmed A.
Published: April 2023

Atomoxetine (ATO) belongs to psychoanaleptic drugs and is utilized in attention-deficit hyperactivity syndrome treatment. In this study, two facile and selective approaches are implemented for the spectrophotometric analysis of atomoxetine. The two approaches rely on charge transfer formed between ATO base (n-donor) with p-chloranil and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ; π-acceptor). The generated complexes exhibit absorption intensity maxima at 550 and 460 nm in acetonitrile for p-chloranil and DDQ in the order. Under the optimum reaction condition, Beer’s law was followed for p-chloranil and DDQ at concentrations of 30–320 and 10–80 µg mL− 1, respectively. The ICH guidelines were followed for work validation, and the outcomes were excellent and satisfactory. The assessment of ATO in pharmaceutical capsules using the suggested procedures was successful, and the results were contrasted with those obtained using a different published method to show accuracy and precision. Additionally, the two methods were used to assess the homogeneity of ATO content in the commercialized capsule.
Pilot study: validity and reliability of textile insoles used to measure the characteristics of landing tasks during rehabilitation and artistic gymnastics
Authors: Schümperlin Delia , Schärer Christoph , Kalberer Luzia , Ferguson Stephen J. , Lorenzetti Silvio R.
Published: April 2023

Objectives

Artistic gymnastics is a sport where most athletes start at an early age and training volumes are high. Hence, overuse and acute injuries are frequent due to the load endured during landing tasks. During landing, the ground reaction force (GRF) is up to 15.8 times the body weight and therefore reliable GRF measurements are crucial. The gold standard for GRF measurements are force plates. As force plates are mostly used in a constrained laboratory environment, it is difficult to measure the GRF in representative training settings. Textile insoles (novel GmbH, Munich, Germany) exist, which can be used to measure dynamic GRF. Hence, the motivation of this study is to test the validity and reliability of these insoles during landing tasks. GRF was measured during four different exercises, in two test subjects and compared to concurrent force plate data.

Results

Twelve out of 16 statistical parametric mapping plots showed no significant difference between the measured force curves of insoles and force plates. Across conditions, the root mean square error of the maximal vertical GRF was 21 N/kg and an impulse 0.4 Ns/kg. The intraclass correlation coefficient (ICC 2,1) ranged from 0.02 to 0.76 for maximal vertical GRF and from − 0.34 to 0.76 for impulse. The insoles are a valid measurement tool for GRF curve progression and impulse during landing but underestimate the maximal vertical GRF.
Bilateral distal Achilles tendon sleeve avulsion: a case report
Authors: Mohd Rothi Illina , Åkerback Mikael , Bister Ville
Published: April 2023

Background

While Achilles tendon rupture is a common injury sustained especially in sporting events, distal Achilles tendon rupture is less common. Even rarer is a bilateral traumatic distal Achilles tendon sleeve rupture, with outcomes of such injury unknown. The following case report describes this rare injury, not reported to date elsewhere.

Case

A 57-year-old Finnish man with no predisposing medical history had a traumatic bilateral distal Achilles tendon sleeve avulsion injury. Clinical and radiological evaluation confirmed the diagnosis. Treatment included suture anchors in a modified suture bridge style with customized rehabilitation protocol postoperatively. Symptoms continued to be relieved at 1 year postoperatively.

Conclusion

A modified suture bridge style and meticulous rehabilitation protocol including motivated patient contributed to very satisfying results in this very rare bilateral injury.
New tools for the investigation of muscle fiber-type spatial distributions across histological sections
Authors: Redmond Anna K. , Davies Tilman M. , Schofield Matthew R. , Sheard Philip W.
Published: April 2023

Background

The functional and metabolic properties of skeletal muscles are partly a function of the spatial arrangement of fibers across the muscle belly. Many muscles feature a non-uniform spatial pattern of fiber types, and alterations to the arrangement can reflect age or disease and correlate with changes in muscle mass and strength. Despite the significance of this event, descriptions of spatial fiber-type distributions across a muscle section are mainly provided qualitatively, by eye. Whilst several quantitative methods have been proposed, difficulties in implementation have meant that robust statistical analysis of fiber type distributions has not yielded new insight into the biological processes that drive the age- or disease-related changes in fiber type distributions.

Methods

We review currently available approaches for analysis of data reporting fast/slow fiber type distributions on muscle sections before proposing a new method based on a generalized additive model. We compare current approaches with our new method by analysis of sections of three mouse soleus muscles that exhibit visibly different spatial fiber patterns, and we also apply our model to a dataset representing the fiber type proportions and distributions of the mouse tibialis anterior.

Results

We highlight how current methods can lead to differing interpretations when applied to the same dataset and demonstrate how our new method is the first to permit location-based estimation of fiber-type probabilities, in turn enabling useful graphical representation.

Conclusions

We present an open-access online application that implements current methods as well as our new method and which aids the interpretation of a variety of statistical tools for the spatial analysis of muscle fiber distributions.
Feasibility of conducting qualitative research with persons living with dementia and their caregivers during a home-delivered meals pilot trial
Authors: Gadbois Emily A. , Bunker Jennifer N. , Hilgeman Michelle , Shield Renee , McAuliff Kathleen E. , Mills Whitney , Thomas Kali
Published: April 2023

Background

Among older adults, food insecurity is associated with poor health status and health outcomes; people living with dementia (PLWD) are at increased risk for insecurity. Approaches to addressing food insecurity among homebound older adults include two modes of home-delivered meals: (1) meals delivered daily to participants’ homes by a volunteer or paid driver who socializes with the client or (2) frozen meals that are mailed to participants’ homes. Research has not examined benefits of these meals for PLWD or their caregivers nor compared the effectiveness of these two approaches in reducing food insecurity. The objective of this study was to test the processes for recruiting and engaging in qualitative research with PLWD and caregivers in an effort to understand the context, implementation, and mechanisms of impact by which relationships between meal delivery and outcomes may be achieved in preparation for a larger, follow-on study.

Methods

This is a qualitative sub-study of a pilot, multisite, two-arm pragmatic feasibility trial comparing the effect of two modes of meal delivery on nursing home placement among 243 PLWD. In this sub-study, we tested recruitment and enrollment procedures and piloted interview guides among a subset of participants and caregivers.

Results

We recruited and conducted interviews with nine PLWD and seven caregivers. In testing the informed consent process, all participants were able to consent to be interviewed, and PLWD all demonstrated capacity to consent. We successfully used a cognitive screener to obtain scores of cognitive impairment for PLWD and observed scores indicating a broad range of function. Our interview guides successfully resulted in information about the context, implementation, and mechanisms of impact for meal delivery during the pilot.

Conclusions

In addition to establishing feasibility for the future trial, the substantive findings identified through the qualitative interviews provide an initial understanding of the contextual factors for meal delivery and the potential mechanisms of impact across meal delivery types that warrant further examination in a full-scale trial. Findings from our study provide crucial pilot data to support a follow-on trial to understand how to address food insecurity among PLWD.

Name of the registry

ClinicalTrials.gov

Trial registration

NCT04850781

Date of registration

April 20, 2021, retrospectively registered

https://clinicaltrials.gov/ct2/show/NCT04850781
Long-Term Outcomes of Parathyroid Autografts in Primary Hyperparathyroidism
Authors: Chuki Elias , Graf Akua , Ninan Anisha , Tora Rana , Abijo Tomilowo , Bliss Lynn , Nilubol Naris , Weinstein Lee S , Agarwal Sunita K , Simonds William F , Jha Smita
Published: April 2023

Context

Autologous implantation of parathyroid tissue is frequently utilized after parathyroidectomy in patients with heritable forms of primary hyperparathyroidism (PHPT). Data on long-term functional outcome of these grafts is sparse.

Objective

To investigate long-term outcomes of parathyroid autografts.

Methods

Retrospective study of patients with PHPT who underwent parathyroid autografts from 1991 to 2020.

Results

We identified 115 patients with PHPT who underwent 135 parathyroid autografts. Median follow-up duration since graft was 10 (4-20) years. Of the 111 grafts with known functional outcome, 54 (49%) were fully functional, 13 (12%) partially functional, and 44 (40%) nonfunctional at last follow-up. Age at time of graft, thymectomy prior to autograft, graft type (delayed vs immediate), or duration of cryopreservation did not predict functional outcome. There were 45 (83%) post-graft PHPT recurrences among 54 fully functional grafts at a median duration of 8 (4-15) years after grafting. Surgery was performed in 42/45 recurrences, but cure was attained in 18/42 (43%) only. Twelve of 18 (67%) recurrences were graft-related while remaining 6 (33%) had a neck or mediastinal source. Median time to recurrence was 16 (11-25) years in neck or mediastinal source vs 7 (2-13) years in graft-related recurrences. Median parathyroid hormone (PTH) gradient was significantly higher at 23 (20-27) in graft-related recurrence vs 1.3 (1.2-2.5) in neck or mediastinal source (P = .03).

Conclusions

Post-graft recurrence of PHPT occurs frequently within the first decade after graft and is challenging to localize. Time to recurrence after graft is significantly shorter and PTH gradient higher for graft-related recurrence.

Clinical Trial Number: NCT04969926
Flexibility is a hidden axis of biomechanical diversity in fishes
Authors: Jimenez Yordano E. , Lucas Kelsey N. , Long John H. , Tytell Eric D.
Published: April 2023

Nearly all fish have flexible bodies that bend as a result of internal muscular forces and external fluid forces that are dynamically coupled with the mechanical properties of the body. Swimming is therefore strongly influenced by the body's flexibility, yet we do not know how fish species vary in their flexibility and in their ability to modulate flexibility with muscle activity. A more fundamental problem is our lack of knowledge about how any of these differences in flexibility translate into swimming performance. Thus, flexibility represents a hidden axis of diversity among fishes that may have substantial impacts on swimming performance. Although engineers have made substantial progress in understanding these fluid–structure interactions using physical and computational models, the last biological review of these interactions and how they give rise to fish swimming was carried out more than 20 years ago. In this Review, we summarize work on passive and active body mechanics in fish, physical models of fish and bioinspired robots. We also revisit some of the first studies to explore flexural stiffness and discuss their relevance in the context of more recent work. Finally, we pose questions and suggest future directions that may help reveal important links between flexibility and swimming performance.