bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining health through a critical materialist political economy lens
Authors: Medvedyuk Stella , Raphael Dennis
Published: October 2023

It has been recognized since antiquity that the organization of society and how it distributes resources are the primary determinants of health. Yet most definitions of health in the academic and practice literatures limit their focus to the individual’s experience of health and functional abilities, neglecting the structures and processes of societies in which the individual is embedded. We draw upon developments in the critical health communication and critical materialist political economy of health literatures to provide a definition of health that directs attention to the role that economic and political systems play in either equitably or inequitably distributing the resources necessary for health. Since these distributions interact with the individual’s unique biological and psychological dispositions and situations to produce health, it is important to identify their sources and means of making their distributions more equitable. Because it is through communication that humans interpret society, themselves, and others, a concise definition of health that draws attention to these societal features and their roles on a day-to-day basis in promoting or threatening health is essential.
Fathers’ and Mothers’ Sexism Predict Less Responsive Parenting Behavior During Family Interactions
Authors: Overall Nickola C. , Cross Emily J. , Low Rachel S. T. , McRae Caitlin S. , Henderson Annette M. E. , Chang Valerie T.
Published: October 2023

Men’s hostile sexism predicts harmful behavior toward women. Yet, most investigations have relied on self-report assessments, and overlooked a critical, consequential behavioral outcome: responsive parenting. The current studies provide the first behavioral evidence of the associations between hostile sexism and parenting. Fathers higher in hostile sexism reported lower authoritative (warm, involved) and higher authoritarian (directive, controlling) parenting attitudes (Study 1). Observing mixed-gender couples and their 5-year-old child engaging in family interactions ( k = 627), fathers and (unexpectedly) mothers higher in hostile sexism exhibited less responsive parenting irrespective of child gender (Studies 1 and 2). Fathers’ higher hostile sexism also was associated with less responsive behavior toward mothers during family interactions (Studies 1 and 2), but the associations with parenting were independent of couple-level behavior. These studies emphasize the importance of behavioral assessments and advance understanding of the harm both men’s and women’s hostile sexism may have for parents and children.
Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials
Authors: Yang Juan , Lim Kia Hui , Lim Kia Teng , Woods Jeffrey T. , Mohabbat Arya B. , Wahner-Roedler Dietlind L. , Ganesh Ravindra , Bauer Brent A.
Published: October 2023

Background:

Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking.

Objective:

This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review.

Design:

Systematic review of randomized controlled trials (RCTs).

Methods:

A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane ‘risk of bias’ tool. A qualitative analysis was conducted due to heterogeneity of included studies.

Results:

A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program.

Conclusion:

CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.
A mobile-based airway clearance care system using deep learning-based vision technology to support personalized home-based pulmonary rehabilitation for COAD patients: Development and usability testing
Authors: Su Jun-Ming , Chen Kuan-Yuan , Wu Sheng-Ming , Lee Kang-Yun , Ho Shu-Chuan
Published: October 2023

Background

Excessive mucus secretion is a serious issue for patients with chronic obstructive airway disease (COAD), which can be effectively managed through postural drainage and percussion (PD + P) during pulmonary rehabilitation (PR). Home-based (H)-PR can be as effective as center-based PR but lacks professional supervision and timely feedback, leading to low motivation and adherence. Telehealth home-based pulmonary (TH-PR) has emerged to assist H-PR, but video conferencing and telephone calls remain the main approaches for COAD patients. Therefore, research on effectively assisting patients in performing PD + P during TH-PR is limited.

Objective

This study developed a mobile-based airway clearance care for chronic obstructive airway disease (COAD-MoAcCare) system to support personalized TH-PR for COAD patients and evaluated its usability through expert validation.

Methods

The COAD-MoAcCare system uses a mobile device through deep learning-based vision technology to monitor, guide, and evaluate COAD patients’ PD + P operations in real time during TH-PR programs. Medical personnel can manage and monitor their personalized PD + P and operational statuses through the system to improve TH-PR performance. Respiratory therapists from different hospitals evaluated the system usability using system questionnaires based on the technology acceptance model, system usability scale (SUS), and task load index (NASA-TLX).

Results

Eleven participant therapists were highly satisfied with the COAD-MoAcCare system, rating it between 4.1 and 4.6 out of 5.0 on all scales. The system demonstrated good usability (SUS score of 74.1 out of 100) and a lower task load (NASA-TLX score of 30.0 out of 100). The overall accuracy of PD + P operations reached a high level of 97.5% by comparing evaluation results of the system by experts.

Conclusions

The COAD-MoAcCare system is the first mobile-based method to assist COAD patients in conducting PD + P in TH-PR. It was proven to be usable by respiratory therapists, so it is expected to benefit medical personnel and COAD patients. It will be further evaluated through clinical trials.
Analysis of Sectoral Outcomes and Institutional Quality Nexus in Sub-Saharan Africa
Authors: Ekeocha Davidmac O. , Ogbuabor Jonathan E. , Ekeocha Patterson C. , Orji Anthony
Published: October 2023

Following the need for more recent rigorous empirical evidence on the role of institutions at sectoral level as well as the conflicting empirical evidences on the institutions-growth relationship in Africa, this study investigated the sectoral impacts of institutional quality in Sub-Saharan Africa (SSA). The study also revisited the role of institutions in the aggregate economy. The system GMM estimation procedure and a panel of 42 SSA countries were used over the period 2010 to 2018. The results indicate that contrary to the widely held view that institutions foster growth and development, the role of institutional quality in sectoral and aggregate economic performance in SSA generally remained muted. However, the results indicate that initial level of real GDP and labor are robust drivers of growth, particularly in the aggregate economy. The study therefore concludes that the sub-region requires institutional reform, enhanced human capital development and capital accumulation to drive sectoral and aggregate economic performance in SSA.

JEL Classification: N20; F43; C23; N17
Co-movement Between NIFTY Spot and Futures Indices: A Time–Frequency Analysis Using Wavelet
Authors: Katoch Rupinder , Batra Shilpa
Published: October 2023

Appreciation of the impact of spot and futures markets on each other and their respective function in price discovery is the central idea of this study’s microstructure design. The volatility spillover and co-movement between the NIFTY spot and futures indices during the period of 2011–2021 are investigated. Maximal overlap discrete wavelet transformation (MODWT)-based DCC GARCH and Diebold and Yilmaz (2012) models have been applied to understand the dynamic associations and spillovers between returns of NIFTY spot and futures indices. To uncover the time-varying vibrant communications among the markets at diverse scales, a wavelet coherence technique has been used. The study found that index prices have a strong and significant dynamic conditional correlation at all scales, and there is diffusion of news in the short as well as long terms. The study uses novel granular wavelet-based research models to decode time–frequency varying behavioural patterns of spot and futures stock indices of India. It highlights the relationships between variables of interest over a range of timescales and allows market participants to rapidly evaluate their investment horizons at varied frequency band scales when building portfolio choices. Therefore, the study offers added understanding to investors and risk managers.

JEL Classifications: G11, G12, G13, G14
A Systematic Review of Screw and Suture Button Glenoid Augmentation Constructs
Authors: Manfredi John N. , Schick Samuel , Paul Kyle D. , Elphingstone Joseph W. , Sowell Josiah , Lameka Megan , Brabston Eugene W. , Momaya Amit M. , Ponce Brent A.
Published: October 2023

Background:

Glenohumeral dislocations often lead to glenoid bone loss and recurrent instability, warranting bony augmentation. While numerous biomechanical studies have investigated fixation methods to secure a graft to the glenoid, a review of available constructs has yet to be performed.

Purpose:

To synthesize the literature and compare the biomechanics of screw and suture button constructs for anterior glenoid bony augmentation.

Study Design:

Systematic review.

Methods:

A systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. There were 2 independent reviewers who performed a literature search using the PubMed, Embase, and Google Scholar databases of studies published between 1950 and 2020. Studies were included that compared the biomechanical outcomes of fixation for the treatment of anterior shoulder instability with glenoid bone loss.

Results:

Overall, 13 of the 363 studies screened met the inclusion criteria. The included studies measured the biomechanical strength of screws or suture buttons on a cadaveric or synthetic Latarjet construct. Screws and suture buttons were biomechanically similar, as both constructs exhibited comparable loads at failure and final displacement. Screw type (diameter, threading, or composition) did not significantly affect construct strength, and double-screw fixation was superior to single-screw fixation. Additionally, 2 screws augmented with a small plate had a higher load at failure than screws that were not augmented. Unicortical double-screw fixation was inferior to bicortical double-screw fixation, although construct strength did not significantly decrease if 1 of these screws was unicortical. Further, 2 screws inserted at 15° off axis experienced significantly higher graft displacement and lower ultimate failure loads than those inserted at 0° parallel to the glenoid.

Conclusion:

Suture buttons provided comparable strength to screws and offer an effective alternative to reduce screw-related complications. Augmentation with a small plate may clinically enhance construct strength and decrease complications through the dispersion of force loads over a greater surface area. Differences in screw type did not appear to alter construct strength, provided that screws were placed parallel to the articular surface and were bicortical.
Contribution of the Medial Hamstrings to Valgus Stability of the Knee
Authors: Vermorel Pierre-Henri , Testa Rodolphe , Klasan Antonio , Putnis Sven E. , Philippot Rémi , Sonnery-Cottet Bertrand , Neri Thomas
Published: October 2023

Background:

Multiligament knee injuries involving the medial side are common. When performing surgical reconstruction, use of the medial hamstrings (HS) as grafts remains controversial in this setting.

Purpose:

To determine the role of the medial HS in stabilizing the valgus knee for different types of medial-sided knee injury.

Study Design:

Controlled laboratory study.

Methods:

A biomechanical study on 10 cadaveric knees was performed. Valgus load (force moment of 10 N/m) was applied at 0°, 30°, and 60° of flexion, and the resultant rotation was recorded using an optoelectronic motion analysis system. Measurements were repeated for 4 different knee states: intact knee, superficial medial collateral ligament (sMCL) injury, deep medial collateral ligament (dMCL) injury, and posterior oblique ligament (POL) injury. For each state, 4 loading conditions (+ loaded; – unloaded) of the semitendinosus (ST) and gracilis (GRA) tendons were tested: ST+/GRA+, ST+/GRA–, ST–/GRA+, and ST–/GRA–.

Results:

At 0° of flexion, combined unloading of the ST and GRA (ST–/GRA–) increased valgus laxity on the intact knee compared with the ST+/GRA+ condition ( P < .05). For all medial-sided injury states (isolated sMCL; combined sMCL and dMCL; and combined sMCL, dMCL, and POL damage), ST–/GRA– increased valgus laxity at 0° and 30° of flexion versus ST+/GRA+ ( P < .05 for all). The absolute value of valgus laxity increased with the severity of medial-sided ligament injury. Isolated ST unloading increased valgus laxity for the intact knee and the MCL-injured knee (combined sMCL and dMCL) at 0° of flexion ( P < .05 vs ST+/GRA+). Isolated unloading of the GRA had no effect on valgus knee stability.

Conclusion:

The medial HS tendons contributed to the stabilization of the knee in valgus, and this was even more important when the medial side was severely affected (POL damage). This stabilizing effect was greater between 0° and 30°, in which the POL is the main valgus stabilizer.

Clinical Relevance:

When deciding on graft selection for multiligament knee injury reconstruction, the surgeon should be aware of the effect of harvesting the medial HS tendon on valgus laxity.
Unpacking the Art of Customer Complaint Handling in Spanish and British Telecom Emails: A Cross-Cultural Webcare Study With a Human Touch
Authors: Elektra Van Herck Rebecca , Vangehuchten Lieve
Published: October 2023

In spite of the rise of new media in a B2C context, companies still prefer to handle complaints privately. As such, many complaints are handled via email resulting in a professional communication genre of its own. In this study we performed a cross-cultural genre analysis to understand the specific discourse structure of the moves within response mails to complaints, on the one hand, and the importance of the communicative function of Conversational Human Voice within this genre, on the other. With this aim, we collected authentic organizational email replies to complaints from telecom companies active in the UK and Spain (36 and 44 emails respectively). The results indicate that the British and Spanish data sets show a similar discourse structure in terms of move frequency. The submoves that are prototypical for all data sets are Greeting, Explanation, Conclusion, and the closing submoves Sign-off and Signature. The data sets differ mainly in their frequency for the interpersonal submoves Empathy, Gratitude, and Apology, which are more prevalent in the English corpus, and the more business-oriented moves, such as Contact reason, Marketing, and Future contact, which are mainly present in the Spanish corpus. This suggests that organizational email replies to complaints are a rather conventionalized genre, with some linguacultures putting more effort in company-customer interactions by using more interpersonal submoves. Regarding the cross-cultural analysis of the expression of Conversational Human Voice we observed an influence of the respective linguacultures in the sense that the Spanish data are less personal and less invitational than the English mails, although they present more empathetic intensifiers. Furthermore, both data sets show only a limited extent of informal language. We evaluate these findings in the light of previous work.
When a pandemic and epidemic collide: Lessons learned about how system barriers can interrupt implementation of addiction research
Authors: Sharp Amanda , Carlson Melissa , Vroom Enya B. , Rigg Khary , Hills Holly , Harding Cassandra , Moore Kathleen , Schuman-Olivier Zev
Published: October 2023

Background

Telehealth technologies are now featured more prominently in addiction treatment services than prior to the COVID-19 pandemic, but system barriers should be carefully considered for the successful implementation of innovative remote solutions for medication management and recovery coaching support for people with opioid use disorder (OUD).

Method

The Centers for Disease Control and Prevention funded a telehealth trial prior to the COVID-19 pandemic with a multi-institution team who attempted to implement an innovative protocol during the height of the pandemic in 2020 in Tampa, Florida. The study evaluated the effectiveness of a mobile device application, called MySafeRx, which integrated remote motivational recovery coaching with daily supervised dosing from secure pill dispensers via videoconference, on medication adherence during buprenorphine treatment. This paper provides a participant case example followed by a reflective evaluation of how the pandemic amplified both an existing research-to-practice gap and clinical system barriers during the implementation of telehealth clinical research intervention for patients with OUD.

Findings

Implementation challenges arose from academic institutional requirements, boundaries and role identity, clinical staff burnout and lack of buy-in, rigid clinical protocols, and limited clinical resources, which hampered recruitment and intervention engagement.

Conclusions

As the urgency for feasible and effective telehealth solutions continues to rise in response to the growing numbers of opioid-related deaths, the scientific community may use these lessons learned to re-envision the relationship between intervention implementation and the role of clinical research toward mitigating the opioid overdose epidemic.
Ibrutinib-based therapy reinvigorates CD8+ T cells compared to chemoimmunotherapy: immune monitoring from the E1912 trial
Authors: Papazoglou Despoina , Wang Xin Victoria , Shanafelt Tait D. , Lesnick Connie E. , Ioannou Nikolaos , De Rossi Giulia , Herter Sylvia , Bacac Marina , Klein Christian , Tallman Martin S. , Kay Neil E. , Ramsay Alan G.
Published: October 2023

Bruton tyrosine kinase inhibitors (BTKis) that target B-cell receptor signaling have led to a paradigm shift in chronic lymphocytic leukemia (CLL) treatment. BTKis have been shown to reduce abnormally high CLL-associated T-cell counts and the expression of immune checkpoint receptors concomitantly with tumor reduction. However, the impact of BTKi therapy on T-cell function has not been fully characterized. Here, we performed longitudinal immunophenotypic and functional analysis of pretreatment and on-treatment (6 and 12 months) peripheral blood samples from patients in the phase 3 E1912 trial comparing ibrutinib-rituximab with fludarabine, cyclophosphamide, and rituximab (FCR). Intriguingly, we report that despite reduced overall T-cell counts; higher numbers of T cells, including effector CD8+ subsets at baseline and at the 6-month time point, associated with no infections; and favorable progression-free survival in the ibrutinib-rituximab arm. Assays demonstrated enhanced anti-CLL T-cell killing function during ibrutinib-rituximab treatment, including a switch from predominantly CD4+ T-cell:CLL immune synapses at baseline to increased CD8+ lytic synapses on-therapy. Conversely, in the FCR arm, higher T-cell numbers correlated with adverse clinical responses and showed no functional improvement. We further demonstrate the potential of exploiting rejuvenated T-cell cytotoxicity during ibrutinib-rituximab treatment, using the bispecific antibody glofitamab, supporting combination immunotherapy approaches.
Chronic active Epstein-Barr virus disease originates from infected hematopoietic stem cells
Authors: Wang Jingshi , Su Min , Wei Na , Yan Huanyu , Zhang Jia , Gong Yi , Wu Lin , Suolitiken Dina , Pi Yubo , Song Deli , Chen Leilei , Liu Huan , Yang Shuo , Wang Xi , Wang Zhao
Published: October 2023

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is a lethal syndrome because of persistent EBV infection. When diagnosed as CAEBV, EBV infection was observed in multiple hematopoietic lineages, but the etiology of CAEBV is still elusive. Bone marrow and peripheral cells derived from 5 patients with CAEBV, 1 patient with EBV-associated hemophagocytic lymphohistiocytosis, and 2 healthy controls were analyzed. Multiple assays were applied to identify and characterize EBV-infected cells, including quantitative polymerase chain reaction, PrimeFlow, and single-cell RNA-sequencing (scRNA-seq). Based on scRNA-seq data, alterations in gene expression of particular cell types were analyzed between patients with CAEBV and controls, and between infected and uninfected cells. One patient with CAEBV was treated with allogeneic hematopoietic stem cell transplantation (HSCT), and the samples derived from this patient were analyzed again 6 months after HSCT. EBV infected the full spectrum of the hematopoietic system including both lymphoid and myeloid lineages, as well as the hematopoietic stem cells (HSCs) of the patients with CAEBV. EBV-infected HSCs exhibited a higher differentiation rate toward downstream lineages, and the EBV infection had an impact on both the innate and adaptive immunity, resulting in inflammatory symptoms. EBV-infected cells were thoroughly removed from the hematopoietic system after HSCT. Taken together, multiple lines of evidence presented in this study suggest that CAEBV disease originates from the infected HSCs, which might potentially lead to innovative therapy strategies for CAEBV.
Clinical features and long-term survival in idiopathic pulmonary arterial hypertension with thyroid dysfunction: insights from a national multicentre prospective study
Authors: Qian Yuling , Quan Ruilin , Chen Xiaoxi , Zhang Gangcheng , Yang Yuanhua , Chen Yucheng , Yu Zaixin , Gu Qing , Xiong Changming , Han Huijun , He Jianguo
Published: October 2023

Background

Our objective was to clarify the characteristics and long-term survival of idiopathic pulmonary arterial hypertension (IPAH) patients with thyroid dysfunction and compare them with IPAH without thyroid dysfunction.

Methods

A retrospective analysis was conducted using prospectively collected data. IPAH patients with thyroid dysfunction at baseline were included. Patients with other subgroups of PAH and Group 2–5 pulmonary hypertension were excluded. IPAH patients with euthyroid function were matched 1:1 to IPAH patients with thyroid dysfunction by age and sex.

Results

In total, 148 IPAH patients with thyroid dysfunction were included. Patients with hyperthyroidism, hypothyroidism, subclinical hyperthyroidism and subclinical hypothyroidism accounted for 16.2%, 18.9%, 8.1% and 56.8%, respectively. IPAH patients with hyperthyroidism showed the highest mixed venous oxygen saturation (SvO2) and the lowest pulmonary vascular resistance (PVR) at baseline among subgroups, while patients with subclinical hypothyroidism had the lowestSvO2and highest PVR (p<0.05). Compared with IPAH without thyroid dysfunction, patients with hyperthyroidism (9.14versus13.86 WU; p<0.05) and hypothyroidism (10.70versus13.86 WU; p<0.05) showed significantly lower PVR. The haemodynamic profiles of patients with subclinical hypothyroidism were similar to IPAH with euthyroid function except for lower right atrial pressure (6versus8 mmHg; p=0.009). The long-term survival of patients with clinical thyroid dysfunction was better than IPAH without thyroid dysfunction, while that of those with subclinical diseases was comparable to the latter, even after adjusting for baseline haemodynamics and treatment.

Conclusion

IPAH patients with clinical hyper- and hypothyroidism had better haemodynamics and survival than those without thyroid dysfunction, while patients with subclinical hypothyroidism had similar haemodynamics and survival profiles to the latter.
Prediction of Grinding Force by an Electroplated Grinding Wheel with Orderly-Micro-Grooves
Authors: Mao Cong , Wang Jiali , Zhang Mingjun , Wang Xincheng , Luo Yuanqiang , Tang Weidong , Tang Kun , Bi Zhuming , Hu Yongle , Lin Zhenheng
Published: October 2023

The ability to predict a grinding force is important to control, monitor, and optimize the grinding process. Few theoretical models were developed to predict grinding forces when a structured wheel was used in a grinding process. This paper aimed to establish a single-grit cutting force model to predict the ploughing, friction and cutting forces in a grinding process. It took into the consideration of actual topography of the grinding wheel, and a theoretical grinding force model for grinding hardened AISI 52100 by the wheel with orderly-micro-grooves was proposed. The model was innovative in the sense that it represented the random thickness of undeformed chips by a probabilistic expression, and it reflected the microstructure characteristics of the structured wheel explicitly. Note that the microstructure depended on the randomness of the protruding heights and distribution density of the grits over the wheel. The proposed force prediction model was validated by surface grinding experiments, and the results showed (1) a good agreement of the predicted and measured forces and (2) a good agreement of the changes of the grinding forces along with the changes of grinding parameters in the prediction model and experiments. This research proposed a theoretical grinding force model of an electroplated grinding wheel with orderly-micro-grooves which is accurate, reliable and effective in predicting grinding forces.
N6-methyladenosine modification—a key player in viral infection
Authors: Zhang Xiaoyue , Peng Qiu , Wang Lujuan
Published: October 2023

N6-methyladenosine (m6A) modification is a dynamic, reversible process and is the most prevalent internal modification of RNA. This modification is regulated by three protein groups: methyltransferases (“writers”), demethylases (“erasers”), and m6A-binding proteins (“readers”). m6A modification and related enzymes could represent an optimal strategy to deepen the epigenetic mechanism. Numerous reports have suggested that aberrant modifications of m6A lead to aberrant expression of important viral genes. Here, we review the role of m6A modifications in viral replication and virus–host interactions. In particular, we focus on DNA and RNA viruses associated with human diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV)-1, Epstein–Barr virus (EBV), and Kaposi’s sarcoma-associated herpesvirus (KSHV). These findings will contribute to the understanding of the mechanisms of virus–host interactions and the design of future therapeutic targets for treatment of tumors associated with viral infections.
Redefining serological diagnostics with immunoaffinity proteomics
Authors: Walter Jonathan , Eludin Zicki , Drabovich Andrei P.
Published: October 2023

Serological diagnostics is generally defined as the detection of specific human immunoglobulins developed against viral, bacterial, or parasitic diseases. Serological tests facilitate the detection of past infections, evaluate immune status, and provide prognostic information. Serological assays were traditionally implemented as indirect immunoassays, and their design has not changed for decades. The advantages of straightforward setup and manufacturing, analytical sensitivity and specificity, affordability, and high-throughput measurements were accompanied by limitations such as semi-quantitative measurements, lack of universal reference standards, potential cross-reactivity, and challenges with multiplexing the complete panel of human immunoglobulin isotypes and subclasses. Redesign of conventional serological tests to include multiplex quantification of immunoglobulin isotypes and subclasses, utilize universal reference standards, and minimize cross-reactivity and non-specific binding will facilitate the development of assays with higher diagnostic specificity. Improved serological assays with higher diagnostic specificity will enable screenings of asymptomatic populations and may provide earlier detection of infectious diseases, autoimmune disorders, and cancer. In this review, we present the major clinical needs for serological diagnostics, overview conventional immunoassay detection techniques, present the emerging immunoassay detection technologies, and discuss in detail the advantages and limitations of mass spectrometry and immunoaffinity proteomics for serological diagnostics. Finally, we explore the design of novel immunoaffinity-proteomic assays to evaluate cell-mediated immunity and advance the sequencing of clinically relevant immunoglobulins.
Developmental validation of a high-resolution panel genotyping 639 Y-chromosome SNP and InDel markers and its evolutionary features in Chinese populations
Authors: Zhao Guang-Bin , Miao Lei , Wang Mengge , Yuan Jia-Hui , Wei Lan-Hai , Feng Yao-Sen , Zhao Jie , Kang Ke-Lai , Zhang Chi , Ji An-Quan , He Guanglin , Wang Le
Published: October 2023

Uniparental-inherited haploid genetic marker of Y­chromosome single nucleotide polymorphisms (Y-SNP) have the power to provide a deep understanding of the human evolutionary past, forensic pedigree, and bio-geographical ancestry information. Several international cross-continental or regional Y-panels instead of Y-whole sequencing have recently been developed to promote Y-tools in forensic practice. However, panels based on next-generation sequencing (NGS) explicitly developed for Chinese populations are insufficient to represent the Chinese Y-chromosome genetic diversity and complex population structures, especially for Chinese-predominant haplogroup O. We developed and validated a 639-plex panel including 633 Y-SNPs and 6 Y-Insertion/deletions, which covered 573 Y haplogroups on the Y-DNA haplogroup tree. In this panel, subgroups from haplogroup O accounted for 64.4% of total inferable haplogroups. We reported the sequencing metrics of 354 libraries sequenced with this panel, with the average sequencing depth among 226 individuals being 3,741×. We illuminated the high level of concordance, accuracy, reproducibility, and specificity of the 639-plex panel and found that 610 loci were genotyped with as little as 0.03 ng of genomic DNA in the sensitivity test. 94.05% of the 639 loci were detectable in male-female mixed DNA samples with a mix ratio of 1:500. Nearly all of the loci were genotyped correctly when no more than 25 ng/μL tannic acid, 20 ng/μL humic acid, or 37.5 μM hematin was added to the amplification mixture. More than 80% of genotypes were obtained from degraded DNA samples with a degradation index of 11.76. Individuals from the same pedigree shared identical genotypes in 11 male pedigrees. Finally, we presented the complex evolutionary history of 183 northern Chinese Hans and six other Chinese populations, and found multiple founding lineages that contributed to the northern Han Chinese gene pool. The 639-plex panel proved an efficient tool for Chinese paternal studies and forensic applications.
Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma—randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol
Authors: Modesto Anouchka , Tougeron David , Tremolières Pierre , Ronchin Philippe , Jouve Ariane Darut , Leignel Delphine Argo , Vendrely Véronique , Riou Olivier , Martin-Babau Jérôme , Le Sourd Samuel , Mirabel Xavier , Leroy Thomas , Huguet Florence , Montaigne Lucile , Baumgaertner Isabelle , Deslandres Marion , Moyal Elizabeth , Seva Catherine , Selves Janick , Otal Philippe , Pezzella Veronica , Guimbaud Rosine , Filleron Thomas , Quéro Laurent
Published: October 2023

Background

In case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies. In recent years, several immune checkpoint inhibitors (anti-PD1/anti-PD-L1, anti-Program-Death 1/anti-Program-Death ligand 1) have been approved for the treatment of various solid malignancies including metastatic esophageal cancer. As such, we hypothesized that the addition of an anti-PD-L1 to CRT would provide clinical benefit for patients with locally advanced oesophageal cancer. To assess the efficacy of the anti-PD-L1 durvalumab in combination with CRT and then as maintenance therapy we designed the randomized phase II ARION (Association of Radiochemotherapy with Immunotherapy in unresectable Oesophageal carciNoma- UCGI 33/PRODIGE 67).

Methods

ARION is a multicenter, open-label, randomized, comparative phase II trial. Patients are randomly assigned in a 1:1 ratio in each arm with a stratification according to tumor stage, histology and centre. Experimental arm relies on CRT with 50 Gy in 25 daily fractions in combination with FOLFOX regimen administrated during and after radiotherapy every two weeks for a total of 6 cycles and durvalumab starting with CRT for a total of 12 infusions. Standard arm is CRT alone. Use of Intensity Modulated radiotherapy is mandatory.

The primary endpoint is to increase progression-free survival at 12 months from 50 to 68% (HR = 0.55) (power 90%; one-sided alpha-risk, 10%). Progression will be defined with central external review of imaging.

Ancillary studies are planned

PD-L1 Combined Positivity Score on carcinoma cells and stromal immune cells of diagnostic biopsy specimen will be correlated to disease free survival. The study of gut microbiota will aim to determine if baseline intestinal bacteria correlates with tumor response. Proteomic analysis on blood samples will compare long-term responder after CRT with durvalumab to non-responder to identify biomarkers.

Conclusion

Results of the present study will be of great importance to evaluate the impact of immunotherapy in combination with CRT and decipher immune response in this unmet need clinical situation.

Trial registration

ClinicalTrials.gov, NCT: 03777813.Trial registration date: 5th December 2018.
MEX3C as a potential target for hepatocellular carcinoma drug and immunity: combined therapy with Lenvatinib
Authors: Guo Jinhui , Zhao Jie , Xu Qiuran , Huang Dongsheng
Published: October 2023

Background

The immune microenvironment within hepatocellular carcinoma (HCC) is remarkably intricate. Although the combination of an immune checkpoint inhibitor and Lenvatinib can extend the overall survival of HCC patients, the outcome remains suboptimal.

Methods

We assessed alterations in MEX3C expression during hepatocarcinogenesis by validating multiple databases and subsequently developed a predictive model. Subsequently, we enriched the associated genes of MEX3C to investigate its functional role. We examined the correlation between MEX3C expression levels and immune infiltrating cells. The effects of MEX3C knockdown and Lenvatinib on hepatoma cells were observed by cell function experiments.

Results

MEX3C expression is elevated in HCC compared to normal tissues, and its high expression correlates with poor prognosis. Immune checkpoint expression was elevated in the high MEX3C expression group, concomitant with heightened myeloid-derived suppressor cell (MDSC) expression. The combination of MEX3C knockdown and Lenvatinib demonstrated a stronger inhibitory effect on HCC cells compared to Lenvatinib alone.

Conclusion

MEX3C shows promise as a potential therapeutic target for treating HCC. Furthermore, the combination of MEX3C knockdown and Lenvatinib could offer a novel therapeutic avenue for HCC treatment.
Prevalence and associated risk factors for chronic kidney disease in the elderly physically disabled population in Shanghai, China: a cross-sectional study
Authors: Wu Hengjing , Li Yao , Ren Longbing , Li Jue , Wang Yiyan , Jiang Chenghua , Wu Jing
Published: October 2023

Background

The global prevalence of chronic kidney disease (CKD) in the general population is relatively clear. Our previous study showed that elderly individuals who are physically disabled are more likely to experience kidney function impairment, and the main purpose of this study was to determine the prevalence and risk factors associated with CKD in elderly patients with physical disabilities.

Methods

A total of 2679 elderly individuals with physical disabilities from the 2018 Shanghai Disability Health Survey were screened to calculate the prevalence of CKD. Multiple logistic regression was performed to identify the factors associated with CKD. Detailed subgroup analyses of disability level were also conducted.

Results

We confirmed CKD in 287 of 2679 (10.7%) participants. Female sex, age, history of hypertension, red blood cell count, albumin, urea, and uric acid (UA) were independently correlated with CKD. Age and UA abnormalities were common risk factors for different levels of disabilities.

Conclusion

The prevalence of CKD is higher in the mild level of older physically handicapped individuals. Age and the level of UA should also be considered in this population. The preventive strategies for patients with two levels of elderly disability should have different focuses.
Validation of the Swedish version of the safe environment for every kid (SEEK) parent screening questionnaire
Authors: Engström Maria , Lindqvist Sara , Janson Staffan , Feldman Inna , Dubowitz Howard , Lucas Steven
Published: October 2023

Background

Psychosocial risk factors in the home may impair children’s health and development and increase the risk of maltreatment. The Safe Environment for Every Kid (SEEK) model was developed to provide pediatric primary care professionals with a structured way to identify common psychosocial problems. The SEEK model includes use of the Parent Screening Questionnaire (SEEK-PSQ) at routine preventive child health visits, discussion with parents about their responses and, when indicated, referral to relevant services. The SEEK-PSQ has not previously been available in Swedish. The aim of the present study was to evaluate the psychometric properties of an adapted Swedish version of the SEEK-PSQ (PSQ-S).

Methods

This study is part of a cluster-randomised controlled trial of SEEK in the Swedish child health services. To validate the PSQ-S, parents (n = 852) with children 0–18 months of age were invited to complete a survey including the PSQ-S as well as evidence-based standardized instruments for the targeted psychosocial risk factors: economic worries, depressive symptoms, parental stress, alcohol misuse and intimate partner violence (IPV). Baseline data from 611 (72%) parents were analysed regarding sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each risk factor.

Results

As a whole, the PSQ-S had a sensitivity of 93%, specificity of 52%, PPV of 67% and NPV of 87%. For mothers and fathers combined, sensitivity was 80% for economic worries, 89% for depressive symptoms, 78% for parental stress, 47% for intimate partner violence (IPV) and 70% for alcohol misuse. Specificity was highest for IPV and alcohol misuse (91%) and lowest for depressive symptoms (64%). NPV values were high (81–99%) and PPV values were low to moderate (22–69%) for the targeted problems. Sensitivity was higher for mothers compared to fathers for economic worries, depressive symptoms and IPV. This difference was particularly evident for IPV (52% for mothers, 27% for fathers).

Conclusion

The SEEK-PSQ-S demonstrated good psychometric properties for identifying economic worries, depressive symptoms, parental stress and alcohol misuse but low sensitivity for IPV. The PSQ-S as a whole showed high sensitivity and NPV, indicating that most parents with or without the targeted psychosocial risk factors were correctly identified.

Trial registration

ISRCTN registry, study record 14,429,952 (https://doi.org/10.1186/ISRCTN14429952) Registration date 27/05/2020.
Parents, but not their children, demonstrate greater delay discounting with resource scarcity
Authors: Button Alyssa M. , Paluch Rocco A. , Schechtman Kenneth B. , Wilfley Denise E. , Geller Nancy , Quattrin Teresa , Cook Stephen R. , Eneli Ihouma U. , Epstein Leonard H.
Published: October 2023

Background

Individuals with obesity tend to discount the future (delay discounting), focusing on immediate gratification. Delay discounting is reliably related to indicators of economic scarcity (i.e., insufficient resources), including lower income and decreased educational attainment in adults. It is unclear whether the impact of these factors experienced by parents also influence child delay discounting between the ages of 8 and 12-years in families with obesity.

Methods

The relationship between indices of family income and delay discounting was studied in 452 families with parents and 6–12-year-old children with obesity. Differences in the relationships between parent economic, educational and Medicaid status, and parent and child delay discounting were tested.

Results

Results showed lower parent income (p = 0.019) and Medicaid status (p = 0.021) were differentially related to greater parent but not child delay discounting among systematic responders.

Conclusions

These data suggest differences in how indicators of scarcity influence delay discounting for parents and children, indicating that adults with scarce resources may be shaped to focus on immediate needs instead of long-term goals. It is possible that parents can reduce the impact of economic scarcity on their children during preadolescent years. These findings suggest a need for policy change to alleviate the burden of scarce conditions and intervention to modify delay discounting rate and to improve health-related choices and to address weight disparities.
Determinants of COVID-19-related knowledge and disrupted habits during epidemic waves among women of childbearing age in urban and rural areas of the Malagasy Middle East
Authors: Rakotosamimanana Sitraka , Mangahasimbola Reziky Tiandraza , Ratovoson Rila , Randremanana Rindra Vatosoa
Published: October 2023

Background

With regard to the coronavirus disease (COVID-19) pandemic in Madagascar, little is known about the knowledge, the perceptions and the impacts of this disease on women of childbearing age. People’s knowledge of COVID-19 can have an impact on their attitudes towards seeking care. The aim of the current study is to determine the knowledge of COVID-19 and associated determinants among women of childbearing age in Moramanga.

Methods

A cross-sectional study based on questionnaire administration was used among women of childbearing age. Data collection was conducted from August to October 2021. A scoring method was applied to evaluate their knowledge level and perceptions about COVID-19 and its impacts on their lives. A binary stepwise logistic regression was performed to determine the sociodemographic determinants of their knowledge level about COVID-19.

Results

A total of 885 women of childbearing age from urban and rural Moramanga areas were interviewed. Approximately 49.8% (441/885) lived in urban areas, and 50.2% (444/885) lived in rural areas. Approximately 35.3% (322/885) of the participants had a good level of knowledge of COVID-19. Multivariate analysis showed that the probability of having a good level of knowledge of COVID-19 had a significant statistical association (p value < 0.05) with living in an urban area [AOR: 2.89; 95% CI (1.89–4.42)], telephone ownership [AOR: 1.71; 95% CI (1.16–2.53)], radio ownership [AOR 2.2; 95% CI (1.43–3.38)], watching TV [AOR = 1.95; 95% CI (1.34–2.83)] and reading journal papers [AOR = 3.74 95% CI (1.69–8.27)].

Conclusions

Almost a third of the sampled women of childbearing age had a good level of knowledge of COVID-19. Access to information through telecommunications technologies increases the chances of being better informed about the disease. To avoid the negative repercussions of infectious disease epidemics, it is necessary to improve the awareness of childbearing women about these diseases by taking demographic features of the population into account.
Causal effects of inflammatory bowel diseases on the risk of kidney stone disease: a two-sample bidirectional mendelian randomization
Authors: Zhang Huayang , Huang Yong , Zhang Junyong , Su Huiyi , Ge Chengguo
Published: October 2023

Background

Existing epidemiological observational studies have suggested interesting but inconsistent clinical correlations between inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), and kidney stone disease (KSD). Herein, we implemented a two-sample bidirectional Mendelian randomization (MR) to investigate the causal relationship between IBD and KSD.

Methods

Data on IBD and KSD were obtained from Genome-Wide Association Studies (GWAS) summary statistics and the FinnGen consortium, respectively. Strict selection steps were used to screen for eligible instrumental SNPs. We applied inverse variance weighting (IVW) with the fix-effects model as the major method. Several sensitivity analyses were used to evaluate pleiotropy and heterogeneity. Causal relationships between IBD and KSD were explored in two opposite directions. Furthermore, we carried out multivariable MR (MVMR) to obtain the direct causal effects of IBD on KSD.

Results

Our results demonstrated that CD could increase the risk of KSD (IVW: OR = 1.06, 95% CI = 1.03–1.10, p < 0.001). Similar results were found in the validation group (IVW: OR = 1.05, 95% CI = 1.01–1.08, p = 0.013) and in the MVMR analysis. Meanwhile, no evidence of a causal association between UC and KSD was identified. The reverse MR analysis detected no causal association.

Conclusions

This MR study verified that CD plays a critical role in developing kidney stones and that the effect of UC on KSD needs to be further explored.