bluuebunny/crossref_metadata_2025 huggingface dataset:
A review of artificial intelligence in prostate cancer detection on imaging
Authors: Bhattacharya Indrani , Khandwala Yash S. , Vesal Sulaiman , Shao Wei , Yang Qianye , Soerensen Simon J.C. , Fan Richard E. , Ghanouni Pejman , Kunder Christian A. , Brooks James D. , Hu Yipeng , Rusu Mirabela , Sonn Geoffrey A.
Published: October 2022

A multitude of studies have explored the role of artificial intelligence (AI) in providing diagnostic support to radiologists, pathologists, and urologists in prostate cancer detection, risk-stratification, and management. This review provides a comprehensive overview of relevant literature regarding the use of AI models in (1) detecting prostate cancer on radiology images (magnetic resonance and ultrasound imaging), (2) detecting prostate cancer on histopathology images of prostate biopsy tissue, and (3) assisting in supporting tasks for prostate cancer detection (prostate gland segmentation, MRI-histopathology registration, MRI-ultrasound registration). We discuss both the potential of these AI models to assist in the clinical workflow of prostate cancer diagnosis, as well as the current limitations including variability in training data sets, algorithms, and evaluation criteria. We also discuss ongoing challenges and what is needed to bridge the gap between academic research on AI for prostate cancer and commercial solutions that improve routine clinical care.
Commercial smartwatch with pulse oximeter detects short-time hypoxemia as well as standard medical-grade device: Validation study
Authors: Rafl Jakub , Bachman Thomas E , Rafl-Huttova Veronika , Walzel Simon , Rozanek Martin
Published: October 2022

Objective

We investigated how a commercially available smartwatch that measures peripheral blood oxygen saturation (SpO2) can detect hypoxemia compared to a medical-grade pulse oximeter.

Methods

We recruited 24 healthy participants. Each participant wore a smartwatch (Apple Watch Series 6) on the left wrist and a pulse oximeter sensor (Masimo Radical-7) on the left middle finger. The participants breathed via a breathing circuit with a three-way non-rebreathing valve in three phases. First, in the 2-minute initial stabilization phase, the participants inhaled the ambient air. Then in the 5-minute desaturation phase, the participants breathed the oxygen-reduced gas mixture (12% O2), which temporarily reduced their blood oxygen saturation. In the final stabilization phase, the participants inhaled the ambient air again until SpO2 returned to normal values. Measurements of SpO2 were taken from the smartwatch and the pulse oximeter simultaneously in 30-s intervals.

Results

There were 642 individual pairs of SpO2 measurements. The bias in SpO2 between the smartwatch and the oximeter was 0.0% for all the data points. The bias for SpO2 less than 90% was 1.2%. The differences in individual measurements between the smartwatch and oximeter within 6% SpO2 can be expected for SpO2 readings 90%–100% and up to 8% for SpO2 readings less than 90%.

Conclusions

Apple Watch Series 6 can reliably detect states of reduced blood oxygen saturation with SpO2 below 90% when compared to a medical-grade pulse oximeter. The technology used in this smartwatch is sufficiently advanced for the indicative measurement of SpO2 outside the clinic.

Trial Registration

ClinicalTrials.gov NCT04780724
Co-production as praxis: Critique and engagement from within the university
Authors: Perry Beth
Published: October 2022

This paper takes as its starting point the question of whether there is an inherent tension between co-production and critique. Whilst the former requires engagement, proximity, situatedness, an inclusive definition of expertise and an action-orientation, the latter has traditionally been equated with disengagement, distance, academic expertise and theory-building. Tracing both the critique of co-production and the critique of critique, I suggest that co-producing critique could be one basis for rescuing both from their detractors. Drawing on my experiences in the Realising Just Cities programme (2010–2020), I argue that co-producing critique from within the university requires designing boundary spaces, intermediating between knowledge claims and balancing between articulated and attributed values for co-production. This gives rise to co-production as an epistemic praxis, not method, characterised by boundary work, epistemic choreography and triple shifting. I argue that whilst academics should argue for altogether different kinds of institutions, there is also value in recognising how we are tethered to our institutions. More attention should be paid to choreographing universities into, rather than out, of critical-engaged work, in order to mobilise their privilege and position for social justice.
Decoding the Trends and the Emerging Research Directions of Digital Tourism in the Last Three Decades: A Bibliometric Analysis
Authors: Kalia Prateek , Mladenović Dušan , Acevedo-Duque Ángel
Published: October 2022

Digital technologies have radically changed the tourism industry and gaining a lot of attention from the stakeholders. At present, there is voluminous but fragmented research to cover the various aspects of digital tourism, but a consolidated “big picture” of the extant research is missing. By performing a bibliometric analysis of 827 papers on digital tourism, an attempt has been made to fill this void. The investigation revealed that the management of smart destinations, the internet as a communication and marketing channel, technology and sustainability, and consumer behavior are emerging research directions in digital tourism. Observations regarding little scientific interest and collaborations in regions like Russia and Africa present an opportunity for researchers and businesses to set directions and strategies for the future.

JEL Code M310, Z300, Z310, Z320, Z330
An Empirical Analysis of Supply Chain Competitiveness and Cleaner Production
Authors: Arshed Noman , Hameed Kamran , Saher Asma
Published: October 2022

The increasing world population has placed tremendous pressure on global production systems, which has created a disjoint between the production and sustainability related goals of this sector. Several studies have confirmed this notion via Environmental Kuznets Curve, but this study envisages proposing a possible solution. It is hypothesized that competitive supply chain ecosystems (cluster development & production process sophistication) could help in reducing growth based CO2 emissions globally. An assessment of 135 countries between 2008 and 2018 is conducted. The estimates showed that the supply chain competitiveness has the potential in greenification of our production systems. Here indicators like value chain breadth and cluster development can reduce the CO2 emissions at each production level. Further regions from the geographic map, like North America and Asia Pacific, can adopt a green supply chain from other regions.
Epilepsy and Electroencephalogram Characteristics in Children with Neurofibromatosis Type 1, What We Have Learned from a Tertiary Center Five Years’ Experience
Authors: Khair Abdulhafeez M. , Falchek Stephen , Nikam Rahul , Kaur Gurcharanjeet
Published: October 2022

Introduction: Neurofibromatosis type 1(NF-1) is the commonest neurocutaneous phacomatosis in children. Epilepsy is an infrequent comorbidity. Reports of seizure and Electroencephalogram (EEG) characteristics in children are sparse. Methods: A retrospective review was performed on patients with NF-1 seen between 2016–2020. Patients with co-existing epilepsy were identified. Demographic, clinical, radiological and neurophysiological data were reviewed and analyzed. Results: Out of 118 children with NF1, 16 had epilepsy. 11 patients had focal onset seizures, whereas 5 had generalized onset seizures. Most patients had easy seizure control. Focal epileptiform discharges were the most prevalent EEG abnormality. There was no significant correlation between seizure patterns and presence of intracranial tumors. Conclusion: Epilepsy is a relatively uncommon in pediatric NF-1. Seizures are often of focal semiology and likely to be easily controlled. Focal and multifocal spike epileptiform discharges are the typical interictal EEG findings. Correlation of clinical and EEG findings with intracranial lesions is poor.
Examining the Influence of Algorithmic Message Personalization on Source Credibility and Reputation
Authors: Brown-Devlin Natalie , Lim Hayoung Sally , Tao Jingyue
Published: October 2022

Digital technologies such as AI (Artificial Intelligence) and big data analytics are altering public relations practices such as scanning social media and posting during crises. Crisis scholarship found these practices could potentially yield positive crisis outcomes such as increased reputational measures. However, research has not yet fully outlined the potential risks associated with using these tactics in crisis communication. Guided by situational crisis communication theory (SCCT), this study utilized a 2 (reputation repair strategy: Deny/Apology) x 2 (presence vs. absence of message personalization notification) factorial design experiment to determine how the utilization of algorithmic message personalization might influence reputational and source credibility evaluations during an athlete reputational crisis (ARC). Results revealed that reputation repair strategy selection indirectly influenced stakeholders’ reputation evaluations via source credibility. This relationship was moderated by a notification of personalization. Theoretical and practical insights elucidate how the increased usage of algorithmic-based message personalization influences crisis communication outcomes.
The Enduring Association of a First Pregnancy Abortion with Subsequent Pregnancy Outcomes: A Longitudinal Cohort Study
Authors: Studnicki James , Longbons Tessa , Reardon David C. , Fisher John W. , Harrison Donna J. , Skop Ingrid , Cirucci Christina A. , Craver Christopher , Tsulukidze Maka , Ras Zbigniew
Published: October 2022

Introduction

Multiple abortions are consistently associated with adverse health consequences. Prior abortion is a known risk factor for another abortion.

Objective

To determine the persistence of the association of a first-pregnancy abortion with the likelihood of subsequent pregnancy outcomes.

Methods

Data was extracted for a study population of 5453 continuously eligible Medicaid beneficiaries in states which funded and reported elective abortions 1999–2015. Women age 16 in 1999 were organized into three cohorts based upon the first pregnancy outcome: abortion, birth, natural loss.

Results

Women in the abortion cohort are more likely than those in the birth cohort to experience another abortion rather than a birth or natural loss, and less likely to experience a live birth rather than an abortion or natural loss, for every subsequent pregnancy. The tendency toward abortion (OR 2.99, CL 2.02-4.43) and away from birth (OR 0.49, CL 0.39-0.63) peaks at the sixth pregnancy, but persists throughout the reproductive period ages 16–32. The pattern is reversed, but similarly consistent, for women in the birth cohort. They remain likelier to have another birth rather than an abortion or natural loss in subsequent pregnancies. Compared to the birth cohort, the abortion cohort had 1.35 times as many pregnancies: 4.31 times the abortions, 1.53 times the natural losses, but only 0.52 times the births. They were 4.3 and 5.0 times as likely to have 2-plus and 3-plus abortions, but only 0.47 times and 0.31 times as likely to have 2-plus and 3-plus births. Of the abortion cohort, 37.1% had no births. By contrast, 73.6% of the birth cohort had no abortions.

Conclusion

The first-pregnancy abortion maintains a strong and persistent association with the likelihood of another abortion in subsequent pregnancies, enabling a cascade of adverse events associated with multiple abortions.
Biosynthesized silver nanoparticles and miR34a mimics mediated activation of death receptor in MCF-7 human breast cancer cell lines
Authors: Iqbal Muhammad Javed , Rashid Umer , Javed Zeeshan , Hamid Zara , Imran Komal , Kabeer Ayesha , Raza Shahid , Almarhoon Zainab M. , Reiner Željko , Bagiu Iulia-Cristina , Bagiu Radu Vasile , Sarac Ioan , Sharifi-Rad Javad , Ydyrys Alibek , Daştan Sevgi Durna , Butnariu Monica , Cho William C.
Published: October 2022

Nano-biotechnology-based clinical applications to cure health-related issues have gained huge attention among the scientific community and hold great promise to limit cancer metastasis. In this study, green-derived silver nanoparticles were synthesized by using leaf extract of Litchi chinensis. Characterization of biosynthesized silver nanoparticles was performed by using UV–Vis spectroscopy, FTIR, XRD, EDS, and SEM analysis. The clinical application of green-drive nanoparticles was investigated by using MCF-7 cancer cell lines. MCF-7 breast cancer cell lines were analyzed against three different treatments. (i) Silver nanoparticles (AgNPs), (ii) miR34a mimics and (iii) Co-delivery of AgNPs and miR34a mimics. Cell viability was determined by MTT assay and, extraction of mRNA and cDNA synthesis were performed after successful cellular transfection. qRT-PCR was done for expression analysis of DR4 and DR5 upon exogenous delivery of all 3 treatments. Results indicate that L. chinensis leaves have a significant amount of phenolic and flavonoid contents and also possess massive antioxidant activity. The diameter of nanoparticles was observed in the range of 41–55 nm. It was concluded that green-derived silver nanoparticles can be a potential contributing agent for cancer prevention and are reported to upregulate the expression of DR4 and DR5 by 0.8-folds and 3.7-folds, respectively.
Combining QTL mapping and RNA-Seq Unravels candidate genes for Alfalfa (Medicago sativa L.) leaf development
Authors: Jiang Xueqian , Yang Xijiang , Zhang Fan , Yang Tianhui , Yang Changfu , He Fei , Gao Ting , Wang Chuan , Yang Qingchuan , Wang Zhen , Kang Junmei
Published: October 2022

Background

Leaf size affects crop canopy morphology and photosynthetic efficiency, which can influence forage yield and quality. It is of great significance to mine the key genes controlling leaf development for breeding new alfalfa varieties. In this study, we mapped leaf length (LL), leaf width (LW), and leaf area (LA) in an F1 mapping population derived from a cultivar named ZhongmuNo.1 with larger leaf area and a landrace named Cangzhou with smaller leaf area.

Results

This study showed that the larger LW was more conducive to increasing LA. A total of 24 significant quantitative trait loci (QTL) associated with leaf size were identified on both the paternal and maternal linkage maps. Among them, nine QTL explained about 11.50–22.45% phenotypic variation. RNA-seq analysis identified 2,443 leaf-specific genes and 3,770 differentially expressed genes. Combining QTL mapping, RNA-seq alalysis, and qRT-PCR, we identified seven candidate genes associated with leaf development in five major QTL regions.

Conclusion

Our study will provide a theoretical basis for marker-assisted breeding and lay a foundation for further revealing molecular mechanism of leaf development in alfalfa.
Difficult intubation and postoperative aspiration pneumonia associated with Moebius syndrome: a case report
Authors: Oda Aya , Oue Kana , Oda Yuki , Taguchi Shima , Takahashi Tamayo , Mukai Akari , Doi Mitsuru , Shimizu Yoshitaka , Irifune Masahiro , Yoshida Mitsuhiro
Published: October 2022

Background

Moebius syndrome is a rare congenital disorder characterized by non-progressive palsy of the abducens (VI) and facial (VII) cranial nerves. Its common features include dysfunctions associated with other cranial nerves, orofacial abnormalities, skeletal muscle hypotonia, and other systemic disorders of differing severities. There are several concerns in the perioperative management of patients with Moebius syndrome.

Case presentation

We present a report on the management of general anesthesia of a 14-year-old male patient with Moebius syndrome who was scheduled for mandibular cystectomy. The patient was diagnosed with Moebius syndrome at the age of 7 years based on his clinical manifestations of nerve palsy since birth and cranial nerve palsy of the trigeminal (V), facial (VII), glossopharyngeal (IX), vagus (X), and sublingual nerves (XII). The patient’s oral morphological abnormalities made intubation difficult. He also experienced dysphagia and aspiration pneumonia on a daily basis. Oral secretions were frequently suctioned postoperatively. However, after discharge, the patient developed aspiration pneumonia and was readmitted to the hospital.

Conclusions

The main problem arising when administering general anesthesia to patients with this syndrome is difficult airway management. The oral abnormalities in these patients, such as small jaw and extreme dental stenosis, make mask ventilation and intubation difficult. Furthermore, this syndrome often involves respiratory impairment and dysphagia due to cerebral nerve palsy, so there is a high risk of postoperative respiratory complications. Since multiple organs are affected in patients with Moebius syndrome, appropriate perioperative management strategies must be prepared for these patients.
Association between gout and the development of Parkinson’s disease: a systematic review and meta-analysis
Authors: Fazlollahi Asra , Zahmatyar Mahdi , Alizadeh Hossein , Noori Maryam , Jafari Nasrin , Nejadghaderi Seyed Aria , Sullman Mark J. M. , Gharagozli Koroush , Kolahi Ali-Asghar , Safiri Saeid
Published: October 2022

Background

As a natural antioxidant, uric acid plays a protective role against neurodegenerative disorders, including Parkinson’s disease (PD). Therefore, the risk of PD has been found to be lower in people with hyperuricemia. In this article, we conducted a systematic review and meta-analysis to investigate whether gout affects the future risk of developing PD.

Methods

We searched PubMed, Scopus, the Web of Science, and Google Scholar to find relevant studies, up to March 16, 2022. Studies investigating the risk of PD, following a gout diagnosis, were included if they were cross-sectional, case–control or cohort studies. The Newcastle Ottawa Scale (NOS) checklist was used to assess the quality of all included studies. The meta-analysis was performed using STATA 17.0.

Results

Ten studies were included, which were comprised of three case-controls, six cohort studies and one nested case–control study. We found no significant association between gout and the risk of PD among both sexes (RR = 0.94, 95% CI: 0.86–1.04), although the association was significant for females (RR = 1.09; 95% CI: 1.02–1.17). Subgroup analysis also showed no significant findings by age group, whether they were receiving treatment for gout, study design, quality assessment score, and method of gout ascertainment. In contrast, the studies that defined PD according to the use of drugs showed significant results (RR = 0.82; 95% CI: 0.76–0.89). There was a significant publication bias on the association between gout and PD.

Conclusions

The presence of gout had no significant effect on the risk of subsequently developing PD. Further analyses are recommended to investigate the effects of demographic and behavioral risk factors.
Gray matter reduction in bilateral insula mediating adverse psychiatric effects of body mass index in schizophrenia
Authors: Wu Hui , Dai Guochao , Aizezi Muyeseer , Tang Juan , Zou Ke , Wu Yuhua , Wu Xiaoli
Published: October 2022

Background

Both schizophrenia (SZ) and overweight/obesity (OWB) have shown some structural alterations in similar brain regions. As higher body mass index (BMI) often contributes to worse psychiatric outcomes in SZ, this study was designed to examine the effects of OWB on gray matter volume (GMV) in patients with SZ.

Methods

Two hundred fifty subjects were included and stratified into four groups (n = 69, SZ patients with OWB, SZ-OWB; n = 74, SZ patients with normal weight, SZ-NW; n = 54, healthy controls with OWB, HC-OWB; and n = 53, HC with NW, HC-NW). All participants were scanned using high-resolution T1-weighted sequence. The whole-brain voxel-based morphometry was applied to examine the GMV alterations, and a 2 × 2 full factorial analysis of variance was performed to identify the main effects of diagnosis (SZ vs HC), BMI (NW vs OWB) factors, and their interactions. Further, the post hoc analysis was conducted to compare the pairwise differences in GMV alterations.

Results

The main effects of diagnosis were located in right hippocampus, bilateral insula, rectus, median cingulate/paracingulate gyri and thalamus (SZ < HC); while the main effects of BMI were displayed in right amygdala, left hippocampus, bilateral insula, left lingual gyrus, and right superior temporal gyrus (OWB < NW). There were no significant diagnosis-by-BMI interaction effects in the present study, but the results showed that both SZ and OWB were additively associated with lower GMV in bilateral insula. Moreover, mediation analyses revealed the indirect effect of BMI on negative symptom via GMV reduction in bilateral insula.

Conclusion

This study further supports that higher BMI is associated with lower GMV, which may increase the risk of unfavourable disease courses in SZ.
The FoxP1 gene regulates lung function, production of matrix metalloproteinases and inflammatory mediators, and viability of lung epithelia
Authors: Andreas Alexis , Maloy Abby , Nyunoya Toru , Zhang Yingze , Chandra Divay
Published: October 2022

Background

Genes involved in lung development may become dysregulated in adult life and contribute to the pathogenesis of lung diseases. Multiple genes regulate lung development, including Forkhead box protein P1-4 (FoxP1-4).

Methods

We examined the association between variants in the FoxP1-4 genes and lung function using data from a GWAS that included close to 400,000 individuals and 20 million SNPs.

Results

More than 100 variants in the FoxP1 gene, but none in the FoxP2-4 genes, are associated with lung function. The sentinel variant in the FoxP1 gene associated with FEV1 was rs1499894 (C > T), while the sentinel variant in the FoxP1 gene associated with FVC was rs35480566 (A > G). Those with the T allele instead of the C allele for rs1499894, or the G allele instead of the A allele for rs35480566 had increased FoxP1 mRNA levels in transcriptomic data, higher FEV1 and FVC, and reduced odds of being diagnosed with idiopathic pulmonary fibrosis. Further, knockdown of FoxP1 in lung epithelial cells by RNA interference led to increased mRNA levels for matrix metalloproteinases 1, 2, 3 and pro-inflammatory cytokines IL-6 & IL-8, as well as reduced cell viability after exposure to cigarette smoke—all processes implicated in the pathogenesis of COPD and IPF.

Conclusions

Our results suggest that the protein encoded by the FoxP1 gene may protect against the development of COPD and IPF. A causal role for FoxP1 in the pathogenesis of COPD and IPF may warrant further investigation, and FoxP1 may be a novel therapeutic target for these lung disorders.
CpG island status as an epigenetic alteration for NIS promoter in thyroid neoplasms; a cross-sectional study with a systematic review
Authors: Zarkesh Maryam , Arab Noman , Abooshahab Raziyeh , Heydarzadeh Shabnam , Sheikholeslami Sara , Nozhat Zahra , Salehi Jahromi Marziyeh , Fanaei Seyed Ahmad , Hedayati Mehdi
Published: October 2022

Background

Gene silence via methylation of the CpG islands is cancer's most common epigenetic modification. Given the highly significant role of NIS in thyroid cancer (TC) differentiation, this cross-sectional study aimed to investigate the DNA methylation pattern in seven CpG islands (CpG1-7 including +846, +918, +929, +947, +953, +955, and +963, respectively) of the NIS promoter in patients diagnosed with papillary (PTC), follicular (FTC), and multinodular goiter (MNG). Additionally, a systematic review of the literature was conducted to compare our results with studies concerning methylation of the NIS gene promoter.

Methods

Thyroid specimens from 64 patients met the eligibility criteria, consisting of 28 PTC, 9 FTC, and 27 benign MNG cases. The mRNA of NIS was tested by qRT-PCR. The bisulfite sequencing PCR (BSP) technique was performed to evaluate the promoter methylation pattern of the NIS gene. Sequencing results were received in chromatograph, FASTA, SEQ, and pdf formats and were analyzed using Chromas. The methylation percentage at each position and for each sample was calculated by mC/(mC+C) formula for all examined CpGs; following that, the methylation percentage was also calculated at each CpG site. Besides, a literature search was conducted without restricting publication dates. Nine studies met the eligibility criteria after removing duplicates, unrelated articles, and reviews.

Results

NIS mRNA levels decreased in tumoral tissues of PTC (P = 0.04) and FTC (P = 0.03) patients compared to their matched non-tumoral ones. The methylation of NIS promoter was not common in PTC samples, but it was frequent in FTC (P < 0.05). Significant differences were observed in the methylation levels in the 4th(+ 947), 6th(+ 955), and 7th(+ 963) CpGs sites in the forward strand of NIS promoter between FTC and MNG tissues (76.34 ± 3.12 vs 40.43 ± 8.42, P = 0.004, 69.63 ± 3.03 vs 23.29 ± 6.84, P = 0.001 and 50.33 ± 5.65 vs 24 ± 6.89, P = 0.030, respectively). There was no significant correlation between the expression and methylation status of NIS in PTC and FTC tissues.

Conclusion

Perturbation in NIS promoter’s methylation individually may have a potential utility in differentiating MNG and FTC tissues. The absence of a distinct methylation pattern implies the importance of other epigenetic processes, which may alter the production of NIS mRNA. In addition, according to the reversibility of DNA methylation, it is anticipated that the design of particular targeted demethylation medicines will lead to a novel cancer therapeutic strategy.
Etomoxir, a carnitine palmitoyltransferase 1 inhibitor, combined with temozolomide reduces stemness and invasiveness in patient-derived glioblastoma tumorspheres
Authors: Shim Jin-Kyoung , Choi Seonah , Yoon Seon-Jin , Choi Ran Joo , Park Junseong , Lee Eun Hee , Cho Hye Joung , Lee Suji , Teo Wan-Yee , Moon Ju Hyung , Kim Hyun Sil , Kim Eui Hyun , Cheong Jae-Ho , Chang Jong Hee , Yook Jong In , Kang Seok-Gu
Published: October 2022

Introduction

The importance of fatty acid oxidation (FAO) in the bioenergetics of glioblastoma (GBM) is being realized. Etomoxir (ETO), a carnitine palmitoyltransferase 1 (CPT1) inhibitor exerts cytotoxic effects in GBM, which involve interrupting the FAO pathway. We hypothesized that FAO inhibition could affect the outcomes of current standard temozolomide (TMZ) chemotherapy against GBM.

Methods

The FAO-related gene expression was compared between GBM and the tumor-free cortex. Using four different GBM tumorspheres (TSs), the effects of ETO and/or TMZ was analyzed on cell viability, tricarboxylate (TCA) cycle intermediates and adenosine triphosphate (ATP) production to assess metabolic changes. Alterations in tumor stemness, invasiveness, and associated transcriptional changes were also measured. Mouse orthotopic xenograft model was used to elucidate the combinatory effect of TMZ and ETO.

Results

GBM tissues exhibited overexpression of FAO-related genes, especially CPT1A, compared to the tumor-free cortex. The combined use of ETO and TMZ further inhibited TCA cycle and ATP production than single uses. This combination treatment showed superior suppression effects compared to treatment with individual agents on the viability, stemness, and invasiveness of GBM TSs, as well as better downregulation of FAO-related gene expression. The results of in vivo study showed prolonged survival outcomes in the combination treatment group.

Conclusion

ETO, an FAO inhibitor, causes a lethal energy reduction in the GBM TSs. When used in combination with TMZ, ETO effectively reduces GBM cell stemness and invasiveness and further improves survival. These results suggest a potential novel treatment option for GBM.
Bargaining with patriarchy through the life course: obstacles faced (and overcome) by women leaders in Kerala’s health sector
Authors: Nambiar Devaki , Benny Gloria , Sankar D Hari
Published: October 2022

Background

The COVID-19 pandemic has helped shine the spotlight on the role of women’s leadership in tackling the world’s health and health system challenges. The proportion of women occupying senior leadership positions in the health sector is less compared to males, even as they constitute a vast majority of the work force. The South Indian state of Kerala is an exception to this trend, a phenomenon that we sought to understand and contextualise. We undertook a study to understand the personal and professional journeys of some women leaders in the Kerala health sector to determine the antecedents of their leadership positions, the challenges that came their way in leadership, and strategies adopted to overcome these challenges. We also investigated into how these experiences shaped their styles and approaches to leadership.

Methods

We conducted a qualitative study involving semi-structured in-depth interviews with women leaders. Sixteen women leaders were identified from public records and through peer nomination and interviewed in their language of preference following written informed consent procedures. Interviews focused on participants’ professional and personal trajectories, work-life balance, style of leadership, challenges, enablers, lessons learned in their path, and their vision for the health system. The interviews conducted in Malayalam were transliterated into English and thematically analysed using Atlas.Ti8 software by three researchers.

Results

Our study participants were aged 40 to around 80 years, from 8 out of 14 districts of the state. Women leaders in Kerala’s health sector faced challenges through the life-course: during their early school education, in professional service as well as in their roles as leaders. There were myriad experiences – including gender stereotyping and discrimination at the intersection of gender and other social identities. Women developed manifold ways of overcoming them and evolve unique – and again myriad—leadership styles.

Conclusions

Women leaders in Kerala have faced shared challenges through their life-course to climb up the ranks of leadership; each leader has adopted unique ways of overcoming them and developed similarly unique leadership styles. At each life stage there were bargains with patriarchy – involving family members (often as allies), against formal and informal institutional rules, managers, peers and subordinates., which in turn suggests a feminist consciousness on the part of Kerala women leaders as well as the society in which they are seeking to lead.
Improving cancer immunotherapy by rationally combining oncolytic virus with modulators targeting key signaling pathways
Authors: Zhu Zhi , McGray A. J. Robert , Jiang Weijian , Lu Binfeng , Kalinski Pawel , Guo Zong Sheng
Published: October 2022

Oncolytic viruses (OVs) represent a new class of multi-modal immunotherapies for cancer, with OV-elicited antitumor immunity being key to their overall therapeutic efficacy. Currently, the clinical effectiveness of OV as monotherapy remains limited, and thus investigators have been exploring various combinations with other anti-cancer agents and demonstrated improved therapeutic efficacy. As cancer cells have evolved to alter key signaling pathways for enhanced cell proliferation, cancer progression and metastasis, these cellular and molecular changes offer promising targets for rational cancer therapy design. In this regard, key molecules in relevant signaling pathways for cancer cells or/and immune cells, such as EGFR-KRAS (e.g., KRASG12C), PI3K-AKT-mTOR, ERK-MEK, JAK-STAT, p53, PD-1-PD-L1, and epigenetic, or immune pathways (e.g., histone deacetylases, cGAS-STING) are currently under investigation and have the potential to synergize with OV to modulate the immune milieu of the tumor microenvironment (TME), thereby improving and sustaining antitumor immunity. As many small molecule modulators of these signaling pathways have been developed and have shown strong therapeutic potential, here we review key findings related to both OV-mediated immunotherapy and the utility of small molecule modulators of signaling pathways in immuno-oncology. Then, we focus on discussion of the rationales and potential strategies for combining OV with selected modulators targeting key cellular signaling pathways in cancer or/and immune cells to modulate the TME and enhance antitumor immunity and therapeutic efficacy. Finally, we provide perspectives and viewpoints on the application of novel experimental systems and technologies that can propel this exciting branch of medicine into a bright future.
Eicosanoid lipidome activation in post-mortem brain tissues of individuals with APOE4 and Alzheimer’s dementia
Authors: Ebright Brandon , Assante Isaac , Poblete Roy A. , Wang Shaowei , Duro Marlon V. , Bennett David A. , Arvanitakis Zoe , Louie Stan G. , Yassine Hussein N.
Published: October 2022

Background

Chronic neuroinflammation is one of the hallmarks of late-onset Alzheimer’s disease (AD) dementia pathogenesis. Carrying the apolipoprotein ε4 (APOE4) allele has been associated with an accentuated response to brain inflammation and increases the risk of AD dementia progression. Among inflammation signaling pathways, aberrant eicosanoid activation plays a prominent role in neurodegeneration.

Methods

Using brains from the Religious Order Study (ROS), this study compared measures of brain eicosanoid lipidome in older persons with AD dementia to age-matched controls with no cognitive impairment (NCI), stratified byAPOEgenotype.

Results

Lipidomic analysis of the dorsolateral prefrontal cortex demonstrated lower levels of omega-3 fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and DHA-derived neuroprotectin D1 (NPD-1) in persons with AD dementia, all of which associated with lower measures of cognitive function. A significant interaction was observed between carrying theAPOE4allele and higher levels of both pro-inflammatory lipids and pro-resolving eicosanoid lipids on measures of cognitive performance and on neuritic plaque burden. Furthermore, analysis of lipid metabolism pathways implicated activation of calcium-dependent phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and soluble epoxide hydrolase (sEH) enzymes.

Conclusion

These findings implicate activation of the eicosanoid lipidome in the chronic unresolved state of inflammation in AD dementia, which is increased in carriers of theAPOE4allele, and identify potential therapeutic targets for resolving this chronic inflammatory state.
Increasing brain glucose metabolism by ligustrazine piperazine ameliorates cognitive deficits through PPARγ-dependent enhancement of mitophagy in APP/PS1 mice
Authors: Li Zongyang , Meng Xiangbao , Ma Guoxu , Liu Wenlan , Li Weiping , Cai Qian , Wang Sicen , Huang Guodong , Zhang Yuan
Published: October 2022

PPARγ agonists have been proven to be neuroprotective in vitro and in vivo models of Alzheimer’s disease (AD). In the present study, we identified ligustrazine piperazine derivative (LPD) as a novel PPARγ agonist, which was detected by a dual-luciferase reporter assay system. LPD treatment dose-dependently reduced Aβ40 and Aβ42 levels in PC12 cells stably transfected with APP695swe and PSEN1dE9. Intragastric administration of LPD for 3 months dose-dependently reversed cognitive deficits in APP/PS1 mice. LPD treatment substantially decreased hippocampal Aβ plaques in APP/PS1 mice and decreased the levels of Aβ40 and Aβ42 in vivo and in vitro. Moreover, LPD treatment induced mitophagy in vivo and in vitro and increased brain 18F-FDG uptake in APP/PS1 mice. LPD treatment significantly increased OCR, ATP production, maximal respiration, spare respiratory capacity, and basal respiration in APP/PS1 cells. Mechanistically, LPD treatment upregulated PPARγ, PINK1, and the phosphorylation of Parkin (Ser65) and increased the LC3-II/LC3-I ratio but decreased SQSTM1/p62 in vivo and in vitro. Importantly, all these protective effects mediated by LPD were abolished by cotreatment with the selective PPARγ antagonist GW9662. In summary, LPD could increase brain glucose metabolism and ameliorate cognitive deficits through PPARγ-dependent enhancement of mitophagy in APP/PS1 mice.
Postnatal developmental trajectory of sex-biased gene expression in the mouse pituitary gland
Authors: Hou Huayun , Chan Cadia , Yuki Kyoko E. , Sokolowski Dustin , Roy Anna , Qu Rihao , Uusküla-Reimand Liis , Faykoo-Martinez Mariela , Hudson Matt , Corre Christina , Goldenberg Anna , Zhang Zhaolei , Palmert Mark R. , Wilson Michael D.
Published: October 2022

Background

The pituitary gland regulates essential physiological processes such as growth, pubertal onset, stress response, metabolism, reproduction, and lactation. While sex biases in these functions and hormone production have been described, the underlying identity, temporal deployment, and cell-type specificity of sex-biased pituitary gene regulatory networks are not fully understood.

Methods

To capture sex differences in pituitary gene regulation dynamics during postnatal development, we performed 3’ untranslated region sequencing and small RNA sequencing to ascertain gene and microRNA expression, respectively, across five postnatal ages (postnatal days 12, 22, 27, 32, 37) that span the pubertal transition in female and male C57BL/6J mouse pituitaries (n = 5–6 biological replicates for each sex at each age).

Results

We observed over 900 instances of sex-biased gene expression and 17 sex-biased microRNAs, with the majority of sex differences occurring with puberty. Using miRNA–gene target interaction databases, we identified 18 sex-biased genes that were putative targets of 5 sex-biased microRNAs. In addition, by combining our bulk RNA-seq with publicly available male and female mouse pituitary single-nuclei RNA-seq data, we obtained evidence that cell-type proportion sex differences exist prior to puberty and persist post-puberty for three major hormone-producing cell types: somatotropes, lactotropes, and gonadotropes. Finally, we identified sex-biased genes in these three pituitary cell types after accounting for cell-type proportion differences between sexes.

Conclusion

Our study reveals the identity and postnatal developmental trajectory of sex-biased gene expression in the mouse pituitary. This work also highlights the importance of considering sex biases in cell-type composition when understanding sex differences in the processes regulated by the pituitary gland.
Impact of the national hepatitis B immunization program in China: a modeling study
Authors: Liu Zhixi , Li Mengying , Hutton David W. , Wagner Abram L. , Yao Ye , Zhu Wenlong , Cao Lingsheng , Tang Shenglan , Pan Jinhua , Wang Yesheng , Zhao Qi , Ren Hong , Wang Ying , Wang Weibing
Published: October 2022

Background

Elimination of hepatitis B virus (HBV) is a striking challenge for countries with high or moderate disease burden. Therefore, using China as a practical case to share experiences for similar countries may accelerate the achievement of the WHO 2030 target of 90% reduction in HBV-related incidence. We aim to evaluate the impact of national HBV immunization strategies in China; and the feasibility to achieve WHO 2030 targets under different scenarios.

Methods

We constructed an expanded Susceptible-Exposed-Infectious-Recovered (SEIR) model and decision tree-Markov model to estimate the epidemic of HBV in China, assess the feasibility of 2030 Elimination Goals through the projections and conduct the economic analysis. Least square method was used to calibrate the expanded SEIR model by yearly data of laboratory-confirmed HBV cases from 1990 to 2018. Two models were separately used to evaluate the impact and cost-effectiveness of HBV vaccine by comparing prevalence of chronic HBV infections, quality-adjusted life-years (QALYs), incremental cost effectiveness ratio and benefit–cost ratio (BCR) under various intervention options, providing a basis for exploring new containment strategies.

Results

Between 1990 and 2020, the number of chronic HBV infections decreased by 33.9%. The current status quo would lead to 55.73 million infections (3.95% prevalence) in 2030, compared to 90.63 million (6.42% prevalence) of the “Without the NIP” scenario (NIP: National Immunization Program), 114.78 million (8.13% prevalence) without any interventions. The prevention of mother to child transmission (PMTCT) strategy showed a net benefit as 12,283.50 dollars per person, with BCR as 12.66, which is higher than that of universal vaccination at 9.49. Compared with no screening and no vaccination, the PMTCT strategy could save 7726.03 dollars for each QALY increase.

Conclusions

Our findings proved the HBV vaccination has demonstrated a substantial positive impact on controlling the epidemic of HBV in terms of effectiveness and economy after about 30 years of implementation of the national hepatitis B immunization program which also provided containment experience for high or medium burden countries. As for China, the next step should focus on exploring strategies to improve diagnosis and treatment coverage to reduce the burden of HBV-related deaths and ultimately eliminate HBV.
The Saturne cementless dual-mobility cup grants satisfactory long-term survival
Authors: Gaillard Thierry , Ramos-Pascual Sonia , Saffarini Mo , Piton Jean-Pierre
Published: October 2022

Purpose

To report long-term survival and clinical outcomes of primary total hip arthroplasty (THA) using a Saturne cementless dual-mobility (DM) cup, and investigate whether patient demographics or surgical parameters affect clinical scores.

Methods

A consecutive series of primary THAs implanted with Saturne cementless DM cups between 01/09/2009–31/12/ 2011 was retrospectively assessed. Patients were postoperatively evaluated using modified Harris hip score (mHHS) and forgotten joint score (FJS). Complications, reoperations, and revisions were noted. Regression analyses were performed to determine associations of postoperative mHHS with preoperative and intraoperative variables. Ten-year Kaplan–Meier survival was calculated.

Results

Of 308 patients (308 hips), 111 (36%) had died with their original cups in place, 29 (9%) were lost-to-follow-up, and 5 (2%) required cup revision, leaving a final cohort of 163 (53%) with their original cup in place at a follow-up of ≥ 10 years. Ten-year survival was 98% considering cup revision for any reason as endpoint; 99% considering cup revision for aseptic loosening as endpoint; 96% considering stem revision for any reason as endpoint; and 96% considering any revision as endpoint. The final cohort of 163 patients was assessed at 11 ± 1 years (range, 10–13), mHHS was 85 ± 16 (range, 31–100) and FJS was 84 ± 24 (range, 0–100). Multivariable regression analysis revealed that postoperative mHHS significantly worsened with age (β = -0.48, p = 0.007) and BMI (β = -0.70, p = 0.008), as well as for 22 mm head sizes (β = -6.98, p = 0.046).

Conclusions

The Saturne DM cup granted satisfactory survival and clinical outcomes at a minimum follow-up of 10 years, and resulted in no cases of intra- or extra-prosthetic dislocations.
Comparison of emergency surgical cricothyroidotomy and percutaneous cricothyroidotomy by experienced airway providers in an obese, in vivo porcine hemorrhage airway model
Authors: Karlsson Tomas , Brännström Andreas , Gellerfors Mikael , Gustavsson Jenny , Günther Mattias
Published: October 2022

Background

Emergency front-of-neck airway (eFONA) is a life-saving procedure in “cannot intubate, cannot oxygenate” (CICO). The fastest and most reliable method of eFONA has not been determined. We compared two of the most advocated approaches: surgical cricothyroidotomy and percutaneous cricothyroidotomy, in an obese, in vivo porcine hemorrhage model, designed to introduce real-time physiological feedback, relevant and high provider stress. The primary aim was to determine the fastest method to secure airway. Secondary aims were arterial saturation and partial pressure of oxygen, proxy survival and influence of experience.

Methods

Twelve pigs, mean weight (standard deviation, SD) (60.3 ± 4.1) kg, were anesthetized and exposed to 25–35% total blood volume hemorrhage before extubation and randomization to Seldinger technique “percutaneous cricothyroidotomy” (n = 6) or scalpel-bougie-tube technique “surgical cricothyroidotomy” (n = 6). Specialists in anesthesia and intensive care in a tertiary referral hospital performed the eFONA, simulating an actual CICO-situation.

Results

In surgical cricothyroidotomy vs. percutaneous cricothyroidotomy, the median (interquartile range, IQR) times to secure airway were 109 (IQR 71–130) s and 298 (IQR 128–360) s (P = 0.0152), arterial blood saturation (SaO2) were 74.7 (IQR 46.6–84.2) % and 7.9 (IQR 4.1–15.6) % (P = 0.0167), pO2 were 7.0 (IQR 4.7–7.7) kPa and 2.0 (IQR 1.1–2.9) kPa (P = 0.0667), and times of cardiac arrest (proxy survival) were 137–233 s, 190 (IQR 143–229), from CICO. All six animals survived surgical cricothyroidotomy, and two of six (33%) animals survived percutaneous cricothyroidotomy. Years in anesthesia, 13.5 (IQR 7.5–21.3), did not influence time to secure airway.

Conclusion

eFONA by surgical cricothyroidotomy was faster and had increased oxygenation and survival, when performed under stress by board certified anesthesiologists, and may be an indication of preferred method in situations with hemorrhage and CICO, in obese patients.
Mimicking platelet indices in patients with malaria and dengue hemorrhagic fever: characteristics and clinical applications
Authors: Mon Nant The Su , Tangpukdee Noppadon , Charunwatthana Prakaykaew , Boonnak Kobporn , Krudsood Srivicha , Kano Shigeyuki , Wilairatana Polrat , Leowattana Wattana
Published: October 2022

Background

Although platelet indices are routinely available using automated blood cell counters, the clinical applications of these parameters for malaria and dengue hemorrhagic fever (DHF) have not been substantially implemented. We conducted this study to investigate the potential role of platelet indices as a prognostic marker in adult patients with Plasmodium vivax malaria, Plasmodium falciparum malaria, and DHF admitted to the Hospital for Tropical Diseases, Bangkok, Thailand.

Methods

We enrolled 219 eligible patients, comprising 96 with P. falciparum malaria, 71 with P. vivax malaria, and 52 with DHF. We evaluated the study groups’ baseline clinical features and alterations of platelet indices during the first 4 days of admission.

Results

Upon admission, the initial laboratory findings showed no statistically significant difference in platelet count (PC), plateletcrit (PCT), or platelet distribution width (PDW) between patients with P. vivax and P. falciparum; however, mean platelet volume (MPV) was significantly higher in patients with P. falciparum. Comparisons of the initial platelet indices in malaria and DHF showed that only PC and PCT were significantly lower in DHF. Although MPV in DHF tended to be lower than in malaria, a statistically significant difference was observed only with P. falciparum. Moreover, the results also showed no significant alterations in the platelet indices among the study groups during the first 4 days of admission.

Conclusions and recommendations

Clinical presentations of DHF and malaria are nonspecific and may overlap with other common tropical diseases. Alterations of initial platelet indices may be investigated in P. vivax and P. falciparum malaria mimicking DHF. Although a significant reduction in PC and PCT in DHF might be a clue for differential diagnosis of malaria, the use of MPV and PDW might be impractical. We suggest that appropriate laboratory diagnoses for malaria and dengue infections are still needed for the differential diagnosis of acute febrile patients who have a risk of malaria or dengue infections. To clarify the clinical utility of platelet indices in patients with dengue and malaria, further studies are required that particularly include patients with different severities, geographical areas, and levels of health care settings.