bluuebunny/crossref_metadata_2025 huggingface dataset:
Sociodemographic and health-related factors associated with exclusive breastfeeding in 77 districts of Uganda
Authors: Kimuli Derrick , Nakaggwa Florence , Namuwenge Norah , Nsubuga Rebecca N. , Isabirye Paul , Kasule Kenneth , Katwesige Justine Fay , Nyakwezi Sheila , Sevume Solome , Mubiru Norbert , Amuron Barbara , Bukenya Daraus
Published: December 2023

Background

Uganda surpasses many African nations and the global average in exclusive breastfeeding (EBF) rates. Yet, malnutrition is a critical issue, with stunting impacting roughly 29% of children under 5 years. Enhancing EBF could mitigate such nutritional challenges. This study focused on determining the current EBF prevalence and identifying associated factors across 77 surveyed districts.

Methods

Pooled data from the Lot Quality Assurance Sampling (LQAS) surveys conducted in 77 districts in Uganda during 2021 and 2022 were analyzed. The analysis involved 7,210 mothers of children under 6 months, EBF was considered as the proportion of infants who received breast milk only in the 24 hours before the survey. A mother practicing EBF was (1) currently breastfeeding (2) had not started giving foods other than breastmilk (3) had not given any other probed liquids or (4) semi-solid foods the previous day or night. Multivariable logistic regression was used to identify factors associated with EBF, presenting adjusted odds ratios (aOR) with corresponding 95% confidence intervals at a 5% significance level.

Results

The prevalence of EBF was 62.3%. In the adjusted analysis, EBF was more common among older mothers 20–24 years, 25–29 years and 30 + years (aOR 1.4; 95% CI 1.2,1.6), (aOR 1.4; 95% CI 1.1, 1.6) and (aOR 1.3; 95% CI 1.1, 1.5) respectively compared to teenage mothers. Also, EBF was more likely among mothers who lived in rural areas compared to urban areas (aOR 1.1; 95% CI 1.0, 1.3) and those who attended antenatal care (ANC) (aOR 2.2; 95% CI 1.5, 3.1). On the contrary, EBF was less common for children aged 3–5 months compared to younger (aOR 0.5; 95% CI 0.5, 0.6) and children who had received Vitamin A supplementation (aOR 0.7; 95% 0.6, 0.8).

Conclusion

The study suggests that most districts in Uganda might not have made significant strides in improving EBF rates over the last twenty years, pointing to possible ongoing hurdles that need urgent attention. Particularly, there’s a pressing need to focus on teenage mothers. Maintaining and strengthening programs that advocate EBF, such as ANC, is crucial to bridge the gaps and bring about more equitable rates among different groups.
Clinical and genetic profiles of chinese pediatric patients with catecholaminergic polymorphic ventricular tachycardia
Authors: Yan Yu , Tang Liting , Wang Xiaoqin , Zhou Kaiyu , Hu Fan , Duan Hongyu , Liu Xiaoliang , Hua Yimin , Wang Chuan
Published: December 2023

Backgrounds

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but lethal cardiac ion channelopathy. Delayed diagnosis and misdiagnosis remain a matter of concern due to its rarity and insufficient recognition of this disorder, particularly in developing countries like China.

Aims and methods

We reported six catecholaminergic polymorphic ventricular tachycardia (CPVT) children diagnosed in our center along with a comprehensive review of Chinese pediatric CPVT patients reported in domestic and overseas literature between January 2013 and December 2021 to provide an essential reference for physicians to deepen their understanding of pediatric CPVT.

Results

A total of 95 children with CPVT, including our six patients from 21 medical centers were identified. The median age of symptom onset is 8.7 ± 3.0 years. Diagnosis occurred at a median age of 12.9 ± 6.8 years with a delay of 4.3 ± 6.6 years. Selective beta-blockers (Metoprolol and Bisoprolol) were prescribed for 38 patients (56.7%) and 29 (43.3%) patients received non-selective beta-blocker (Propranolol and Nadolol) treatment. Six patients accepted LCSD and seven received ICD implantation at the subsequent therapy. A total of 13 patients died during the disease course. Of the 67 patients with positive gene test results, variants in RYR2 were 47 (70.1%), CASQ2 were 11 (16.4%), and RYR2 accompanied SCN5A were 7 (10.4%). Patients with CASQ2 gene mutations presented with younger symptom onset age, higher positive family history rate and better prognosis than those with RYR2 mutations.

Conclusion

Chinese pediatric patients with CPVT had a poorer prognosis than other cohorts, probably due to delayed/missed diagnosis, non-standard usage of beta-blockers, unavailability of flecainide, and a lower rate of LCSD and ICD implantation.
Clinical characteristics and outcomes of newly diagnosed patients with human immunodeficiency virus-associated Burkitt lymphoma: the Central and Western China AIDS lymphoma league 002 study (CALL-002 study)
Authors: Zhao Jinrong , Min Haiyan , Huang Yunhong , Chen Yaokai , Wang Min , Xiao Lirong , Wei Guo , Wu Yan , Liu Yao , Zhang Wei
Published: December 2023

Background

Despite the introduction of combined antiretroviral therapy, the clinical outcomes of HIV-associated Burkitt lymphoma (BL) remain poor.

Methods

To evaluate the clinical characteristics, prognostic factors, and outcomes of HIV-associated BL, we conducted a retrospective analysis of patients from multiple centers in China.

Results

The study included 41 patients from 8 medical centers. Among the included population, male patients accounted for 87.8%, with 75.6% in advanced stages. Notably, 46.3% of cases involved bone marrow, while 19.5% involved the central nervous system (CNS). The most commonly used chemotherapy regimen was DA-EPOCH ± R, accounting for 53.6% of cases. The overall response rates for patients receiving DA-EPOCH ± R and R-Hyper-CVAD were 59% and 58.2%, respectively. Interestingly, patients receiving regimens containing rituximab had similar complete remission rates (25% vs. 23.5%) and overall survival time (45.69 ± 11.58 vs. 47.79 ± 11.72 months, P = 0.907) compared to those without rituximab, but differed in progression rates (33.3% vs. 47.1%). For the entire cohort, the 1-year progression-free survival (PFS) and overall survival (OS) rates were 52% and 67%, respectively. CNS involvement was independent risk factors for survival, with 1-year PFS and OS rates of 0% and 38% for patients with CNS involvement, and PFS and OS rates of 66% and 75% for patients without CNS involvement.

Conclusions

HIV-associated BL patients in China have poor prognosis and show limited response to current treatment regimens. The absence of CNS involvement significantly improves clinical outcomes. The use of rituximab is not significantly associated with improved outcomes but can reduce disease progression.
A quantitative analysis of human rights-related attitude changes towards people with mental health conditions and psychosocial, intellectual, or cognitive disabilities following completion of the WHO QualityRights e-training in Ghana
Authors: Poynton-Smith Emma , Orrell Martin , Osei Akwasi , Ohene Sally-Ann , Ansong Joana , Gyimah Leveana , McKenzie Caitlin , Moro Maria Francesca , Drew-Bold Nathalie , Baingana Florence , Carta Mauro Giovanni , Tawiah Priscilla , Brobbey Kwaku , Funk Michelle
Published: December 2023

Background

Despite growing recognition of essential human rights, people with mental health conditions and psychosocial, intellectual, or cognitive disabilities’ rights are known to be frequently violated in mental healthcare worldwide, with common use of coercive practices and limited recognition of people’s right to exercise their legal capacity and make decisions for themselves on treatment and other issues affecting them. To tackle this issue, Ghana adopted the WHO QualityRights Initiative in 2019. This aims to introduce a right-based, person-centred recovery approach within the mental health care system, protecting and promoting the rights of people with mental health conditions, psychosocial, cognitive, and intellectual disabilities in the healthcare context and community.

Methods

E-training (capacity-building) was provided in Ghana across a broad array of stakeholder groups including healthcare professionals, carers, and people with lived experience. The training covered legal capacity, coercion, community inclusion, recovery approach, service environment, and the negative attitudes commonly held by stakeholder groups; it was completed by 17,000 people in Ghana as of December 2021. We assessed the impact of the e-training on attitudes through comparing trainees’ pre- and post-questionnaire responses on 17 items, each measured on a 5-point Likert scale (strongly disagree to strongly agree), such that higher scores indicated negative attitudes towards persons with mental health conditions and psychosocial disabilities as rights holders. Analyses were conducted on two main groups: matched pairs (417 pairs of baseline and follow-up questionnaire responses matched to a high degree of certainty), and the unmatched group (4299 individual completed questionnaire responses).

Results

We assessed the impact of the WHO QualityRights e-training on attitudes: training resulted in highly significant attitude changes towards alignment with human rights, with scores changing by approximately 40% between baseline and follow-up. In particular, attitude changes were seen in items representing treatment choice, legal capacity, and coercion. This change was not affected by age, gender, or background experience.

Conclusions

The QualityRights e-training programme is effective in changing people’s (especially healthcare professionals’) attitudes towards people with mental health conditions and psychosocial, intellectual, or cognitive disabilities: this is a step towards mental healthcare being more with human rights-based worldwide.
Would you choose to be a psychiatrist again? A large-sample nationwide survey of psychiatrists and psychiatry residents in China
Authors: Gu Mengyue , Zheng Liucheng , Gu Jingyang , Wang Song , Shi Yudong , Jiang Feng , Liu Huanzhong , Tang Yi-lang
Published: December 2023

Background

The mental health workforce sustainability in China suffers high rates of attrition and the intention to leave. Among current professionals, the intention to choose the same career is an interesting way to gauge their job satisfaction and other factors, and it may affect the career choices of younger generations. We aimed to survey the intention of psychiatrists and psychiatry residents to choose the same career if they could start over and to identify associated factors.

Methods

We conducted an anonymous survey of psychiatrists in 41 tertiary psychiatric hospitals in China. We collected demographic data, work-related information, the sense of professional identity, job satisfaction, and burnout (Maslach Burnout Inventory), and we specifically asked each participant whether they would choose to be a psychiatrist again if they could.

Results

Among 3,783 psychiatrists we surveyed, one-quarter responded that they would not choose to be a psychiatrist again if they had a choice, with less than half (47.2%) saying they would. Those who would not choose psychiatry again were more likely to have a negative (relative to positive) professional identity (OR = 7.47, P＜0.001, 95%CI: 4.587–12.164); experience job burnout (OR = 2.945, P＜0.001, 95%CI: 2.356–3.681); be dissatisfied with their job (OR = 2.739, P＜0.001, 95%CI: 2.102–3.569) and excessive regulation (OR = 1.819, P＜0.001, 95%CI: 1.487–2.226); have a heavy workload (OR = 1.749, P＜0.001, 95%CI: 1.423–2.149) or a lower income (OR = 1.748, P＜0.001, 95%CI: 1.415–2.161); be married (relative to single) (OR = 1.604, P = 0.004, 95%CI: 1.165–2.208); be dissatisfied with strained doctor-patient relationship (OR = 1.333, P = 0.005, 95%CI: 1.089–1.632); have more night shifts per month (OR = 1.055, P = 0.021, 95%CI: 1.008–1.104) or work longer hours per week (OR = 1.016, P = 0.001, 95%CI: 1.006–1.025).

Conclusion

Among psychiatrists in tertiary hospitals in China, those with a heavier workload, poor sense of professional identity, job dissatisfaction, and burnout were less likely to choose psychiatry again. Policymakers and hospital administrators need to take effective measures to improve psychiatrists’ sense of professional identity and increase their intention to stay.
Clinical and sociodemographic predictors of inpatient admission after presentation in a psychiatric emergency room: an observational study
Authors: Gisy Gianna L. , Toto Sermin , Bleich Stefan , Maier Hannah B. , Seifert Johanna
Published: December 2023

Background

The admission decision after presentation in the psychiatric emergency room (PER) has potentially far-reaching consequences for the patient and the community. In a short amount of time, information must be collected and evaluated for a well-founded admission decision. The present study aimed to identify risk factors associated with inpatient psychiatric admission (IPA) after previous emergency presentation to the PER.

Methods

Electronic patient records for all patients presenting in the PER of Hannover Medical School (MHH) in the year 2022 were retrospectively examined (n = 2580). Out of these, 2387 were included in this study. Two multivariate binary logistic regression analyses were performed to identify risk factors for IPA within sociodemographic, circumstantial and clinical variables.

Results

1300 (54.5%) consultations resulted in IPA. The most significant sociodemographic and circumstantial risk factors for IPA were found to be suicide attempt (depending on method: OR 9.1–17.4), aggressive behavior towards people prior to presentation (OR 2.9, 95% CI 1.7–4.8), previous psychiatric treatment (OR 1.8, 95% CI 1.4–2.3) and transfer from another hospital or medical discipline of MHH as means of presentation (OR 6.3, 95% CI 3.0–13.0). Among psychopathological aspects, suicidal ideation (OR 3.8, 95% CI 2.9–4.9), suicidal intent (OR 116.0, 95% CI 15.9–844.8), disturbance of orientation (OR 3.7, 95% CI 2.5–5.3), delusions (OR 2.3, 95% CI 1.6–3.1), visual hallucinations (OR 2.9, 95% CI 1.6–5.1), hopelessness/despair (OR 2.4, 95% CI 1.7–3.2) and inhibition of drive (OR 1.6, 95% CI 1.3–2.1) were significantly associated with IPA.

Conclusions

The admission decision is a complex process influenced by a multitude of sociodemographic, circumstantial and clinical factors. A deeper understanding of the decision-making process can be used to improve patient care and facilitate the evaluation process in the PER.
Characterization of COVID-19 vaccine clinical trial discussions on the social question-and-answer site Quora
Authors: Xu Qing , McMann Tiana J. , Li Jiawei , Wenzel Christine , Mackey Tim K.
Published: December 2023

Introduction

Throughout the COVID-19 pandemic, underserved populations, such as racial and ethnic minorities, were disproportionately impacted by illness, hospitalization, and death. Equity in clinical trials means that the participants in clinical trials represent the people who are most likely to have the health condition and need the treatment that the trial is testing. Infodemiology approaches examining user conversations on social media platforms have the potential to elucidate specific barriers and challenges related to clinical trial participation, including among racial and ethnic minority populations.

Materials and methods

The study retrospectively collected and analyzed user question and answer posts from Quora in October 2021 using an inductive content coding approach. We also examined user’s publicly available profile metadata to identify racial and ethnic minority users to capture their experiences, attitudes, topics, and discussions of barriers to COVID-19 vaccine trials.

Results

A total of 1073 questions and 7479 answers were collected. A total of 763 questions and 2548 answers were identified as related to COVID-19 vaccine clinical trials. The majority of these online interactions focused on asking questions and sharing knowledge and opinions about COVID-19 vaccine trials, including major topics related to: (a) interpreting whether clinical trial results could be trusted; (b) questions about vaccine efficacy and safety; (c) understanding trial design, regulatory considerations, and vaccine platforms; and (d) questions about trial enrollment, length, and adequate representation. Additionally, four major barriers discussed included: (i) disagreement from users regarding whether clinical trials require representation from different racial and ethnic minorities; (ii) concerns regarding the safety of trials when participating; (iii) lack of knowledge on how to participate in a trial; and (iv) questions of whether participants could withdraw from a trial to access an approved COVID-19 vaccine.

Conclusions

Our study found active user discussions related to COVID-19 vaccine clinical trials on Quora, including those specific to minority health topics and those posted by a smaller group of self-identified racial and ethnic minority online users. Results from this study can help identify barriers to participation among the general public and underrepresented groups while also supporting the design of future outreach strategies to help with recruitment and inclusive trial participation.
Home-based high-intensity interval training improves cardiorespiratory fitness: a systematic review and meta-analysis
Authors: Tsuji Katsunori , Tsuchiya Yosuke , Ueda Hisashi , Ochi Eisuke
Published: December 2023

Background

High-intensity interval training (HIIT) is an effective methods to improve maximal oxygen uptake. However, there is no definitive conclusion about the specific effectiveness of home-based HIIT. This review investigated the effects of home-based HIIT on cardiorespiratory fitness in a systematic review and meta-analysis.

Methods

Four electronic databases were searched (PubMed, Cochran database, Web of Science, Igaku Chuo Zasshi) for studies through March 25, 2023. Eligibility criteria include randomized controlled trials of home-based HIIT in adult people regardless disease or handicaped. Comparisons were made between non-exercise controls, laboratory-based HIIT, and moderate-intensity continuous training (MICT). The primary outcome was defined as cardiorespiratory fitness and the secondary outcome was defined as patient-reported outcomes. The standardized mean difference (SMD) with 95% confidence intervals (CIs) was calculated for quantitative indices. The random-effect model was used as the pooling method.

Results

Two hundred seven studies were identified, and 15 satisfied the inclusion criteria. The meta-analysis for cardiorespiratory fitness showed superiority of home-based HIIT to non-exercise controls (SMD 0.61, 95% CI: 0.21, 1.02). However, no significant difference in cardiorespiratory fitness was observed between home-based HIIT and lab-based HIIT (SMD: -0.35, 95%CI: -0.73, 0.03). Also, no significant difference was observed between the home-based HIIT and MICT (SMD 0.34, 95% CI: -0.05, 0.73).

Conclusion

These results indicated that home-based HIIT was an effective intervention for improving cardiorespiratory fitness in healthy adults and patients. Importantly, this review found no significant differences in cardiorespiratory fitness between home-based HIIT and the group of laboratory HIIT and MICT, highlighting its comparable effectiveness and potential as a practical and valuable exercise intervention.
Efficient bandwidth extension of musical signals using a differentiable harmonic plus noise model
Authors: Grumiaux Pierre-Amaury , Lagrange Mathieu
Published: December 2023

The task of bandwidth extension addresses the generation of missing high frequencies of audio signals based on knowledge of the low-frequency part of the sound. This task applies to various problems, such as audio coding or audio restoration. In this article, we focus on efficient bandwidth extension of monophonic and polyphonic musical signals using a differentiable digital signal processing (DDSP) model. Such a model is composed of a neural network part with relatively few parameters trained to infer the parameters of a differentiable digital signal processing model, which efficiently generates the output full-band audio signal.

We first address bandwidth extension of monophonic signals, and then propose two methods to explicitly handle polyphonic signals. The benefits of the proposed models are first demonstrated on monophonic and polyphonic synthetic data against a baseline and a deep-learning-based ResNet model. The models are next evaluated on recorded monophonic and polyphonic data, for a wide variety of instruments and musical genres. We show that all proposed models surpass a higher complexity deep learning model for an objective metric computed in the frequency domain. A MUSHRA listening test confirms the superiority of the proposed approach in terms of perceptual quality.
Transformative power production futures: citizen jury deliberations in Saskatchewan, Canada
Authors: Hurlbert Margot , Das Tanushree , Vitto Charisse
Published: December 2023

Background

Transforming power production systems to achieve net zero emissions and address climate change will require deep structural changes, partially dependent on community perceptions of the necessary energy transition. The article presents results from 2-day citizen juries held in four communities of Saskatchewan, Canada: Estevan, Swift Current, Regina, and Saskatoon in 2021/22 whose purpose was to determine if place attachment impacts future power production preferences and whether social learning can be achieved. Mixed research methods included a survey before and after the citizen juries and a qualitative analysis of the discussions and outputs.

Results

Research results confirm that while there are common concerns across communities about unbiased information, transparent decision-making, justice/equity concerns, and people's involvement, community-imagined energy futures can be very divergent. Not only place-based attachment, the existent industry and infrastructure surrounding the community impact preferences but also openness to learning and group dynamics contribute. Focused deliberations on the complex problem of climate change advance social learning.

The coal, oil, and gas community of Estevan supported coal, natural gas, and carbon capture and sequestration (CCS) to a substantially larger extent than other communities, even increasing their preference for coal after the citizen jury. Saskatoon chose Small Modular Reactors (SMR) as their top choice, whereas Swift Current switched from preferring natural gas to solar and SMRs.

Conclusions

The findings from the jury sessions suggest changing attitudes toward SMRs as a potential source of energy, as well as a shift from cost considerations to environmental. Future research implications could include differing methodologies and potentially partnering beyond academia. Jurors all expressed the desire for greater government leadership, urging the government to demonstrate accountability, hold large enterprises accountable, and be more proactive in bringing parties together.
Strategies of chemolithoautotrophs adapting to high temperature and extremely acidic conditions in a shallow hydrothermal ecosystem
Authors: Deng Wenchao , Zhao Zihao , Li Yufang , Cao Rongguang , Chen Mingming , Tang Kai , Wang Deli , Fan Wei , Hu Anyi , Chen Guangcheng , Chen Chen-Tung Arthur , Zhang Yao
Published: December 2023

Background

Active hydrothermal vents create extreme conditions characterized by high temperatures, low pH levels, and elevated concentrations of heavy metals and other trace elements. These conditions support unique ecosystems where chemolithoautotrophs serve as primary producers. The steep temperature and pH gradients from the vent mouth to its periphery provide a wide range of microhabitats for these specialized microorganisms. However, their metabolic functions, adaptations in response to these gradients, and coping mechanisms under extreme conditions remain areas of limited knowledge. In this study, we conducted temperature gradient incubations of hydrothermal fluids from moderate (pH = 5.6) and extremely (pH = 2.2) acidic vents. Combining the DNA-stable isotope probing technique and subsequent metagenomics, we identified active chemolithoautotrophs under different temperature and pH conditions and analyzed their specific metabolic mechanisms.

Results

We found that the carbon fixation activities of Nautiliales in vent fluids were significantly increased from 45 to 65 °C under moderately acidic condition, while their heat tolerance was reduced under extremely acidic conditions. In contrast, Campylobacterales actively fixed carbon under both moderately and extremely acidic conditions under 30 − 45 °C. Compared to Campylobacterales, Nautiliales were found to lack the Sox sulfur oxidation system and instead use NAD(H)-linked glutamate dehydrogenase to boost the reverse tricarboxylic acid (rTCA) cycle. Additionally, they exhibit a high genetic potential for high activity of cytochrome bd ubiquinol oxidase in oxygen respiration and hydrogen oxidation at high temperatures. In terms of high-temperature adaption, the rgy gene plays a critical role in Nautiliales by maintaining DNA stability at high temperature. Genes encoding proteins involved in proton export, including the membrane arm subunits of proton-pumping NADH: ubiquinone oxidoreductase, K+ accumulation, selective transport of charged molecules, permease regulation, and formation of the permeability barrier of bacterial outer membranes, play essential roles in enabling Campylobacterales to adapt to extremely acidic conditions.

Conclusions

Our study provides in-depth insights into how high temperature and low pH impact the metabolic processes of energy and main elements in chemolithoautotrophs living in hydrothermal ecosystems, as well as the mechanisms they use to adapt to the extreme hydrothermal conditions.
Preliminary results of the effect of music therapy treatment on anxiety, sadness, physical discomfort, mood, and quality of life in hospitalized onco-haematological patients
Authors: Martí Patricia , Fontanals Irene , Funtané Joel , Canaletas Cristina , Sierra Jorge , Rodés Mariona , Mercadal-Brotons Melissa , González Iria , Novelli Silvana
Published: December 2023

Background

Physical and psychological distress may occur in patients facing an onco-haematological diagnosis and undergoing complex therapies such as intensive chemotherapy, stem cell transplantation, and immunotherapy. Studies have shown the need for incorporating different therapeutic modalities to respond to patients’ physical and psychosocial needs.

Aims

The purpose of this study was to evaluate the effectiveness of music therapy treatment on mood, anxiety, depression, and physical discomfort in hospitalized onco-haematological patients.

Methods

Forty patients were included in this music therapy study from November 2021 to May 2023. Treatment consisted of individual weekly music therapy sessions. Participants completed the following evaluation instruments before and after the intervention: theHospital Anxiety and Depression Scale (HADS),Profile of Mood States—Short Form A-Version (POMS-A), andEuropean Organization for Research and Treatment of Cancer-Quality of Life Core Questionnaire-30 (EORTC QLQ-C30). A three-item numerical rating scale(NRS)for anxiety, sadness, and physical discomfort was administered at the beginning and end of each session (pre-/postsession).

Results

Differences (p < 0.05) were shown in NRS scores for anxiety, sadness, and physical discomfort before and after the music therapy sessions. Quality of life (QoL) was affected in almost all items, and patients could be anxious at a nonclinical level, but they were clinically depressed. EORTC QLQ-C30 scores for insomnia and pain related to the hospitalization process got worse after discharge.

Conclusions

The interim results of our study showed that music therapy sessions can positively change emotional distress and improve the mood of haematological patients after every session. Despite the difficulties and limitations of this study, this preliminary report contributes to a greater understanding of the potential benefits of music therapy in hospitalized onco-haematological patients.
Repressing HIF-1α-induced HDAC9 contributes to the synergistic effect of venetoclax and MENIN inhibitor in KMT2Ar AML
Authors: Ling Qing , Zhou Yutong , Qian Yu , Qian Jiejing , Zhang Yi , Wang Jinghan , Zhu Yanan , Zhou Yile , Wei Juying , Yang Chunmei , Sun Jie , Yu Wenjuan , Jin Jie , Zhang Xiang
Published: December 2023

KMT2A-rearranged acute myeloid leukemia (KMT2Ar-AML) is an aggressive subtype of AML with poor response and prognosis. KMT2Ar-AML has been demonstrated to be sensitive to BCL2 inhibitor venetoclax (VEN), but these patients are unable to benefit from current VEN-based regimen (VEN plus azacitidine or low dose-cytarabine), so a novel and KMT2A rearrangement-specific targeting partner is required, and MENIN inhibitor (MEN1i) is a promising one. Herein, we investigated the effect and mechanism of VEN plus MEN1i in KMT2Ar-AML. Our results showed that VEN and MEN1i exhibited a striking synergistic effect in KMT2Ar-AML cell lines (in vitro), primary KMT2Ar-AML cells (ex vivo), and MOLM13 xenotransplantation model (in vivo). Furthermore, we found that VEN plus MEN1i significantly enhanced apoptotic induction in KMT2Ar-AML cell lines. VEN or MEN1i monotherapy disrupted balance of BCL-2/BCL-XL or down-regulated HOXA9/MEIS1, respectively, but these mechanisms were not further strengthened by their combination. RNA-Sequencing identified that HDAC9 was specifically repressed by VEN plus MEN1i rather than monotherapy. We demonstrated that HDAC9 was indispensable for KMT2Ar-AML proliferation and its repression contributed to proliferation inhibition of VEN plus MEN1i. Moreover, we found that hypoxia induced HDAC9 expression in KMT2Ar-AML, and VEN plus MEN1i inhibited hypoxia pathway, especially HIF-1A, and its target HDAC9. As our results indicated, VEN plus MEN1i-mediated HDAC9 down-regulation was partially dependent on HIF-1A repression in KMT2Ar-AML. Hypoxia induction sensitized KMT2Ar-AML to VEN plus MI-503-mediated proliferation inhibition and apoptosis induction. Therefore, repressing HIF-1A-induced HDAC9 contributed to the synergistic effect of VEN and MEN1i in KMT2Ar-AML.
Dispersal and grain size characteristics of the May 14, 2018 Shinmoedake eruption deposit, Kirishima Volcano, Japan, based on post-eruption field survey and meteorological datasets
Authors: Miyabuchi Yasuo , Sato Eiichi
Published: December 2023

This study describes the dispersal and grain size characteristics of the May 14, 2018 Shinmoedake eruption deposits of Kirishima Volcano in southern Kyushu, southwestern Japan. We discuss the eruption sequence, including the temporal variations in the behavior of the plume, by combining field and meteorological datasets. Following a magmatic activity in 2011 characterized by a substantial change in the eruption style (from subplinian eruptions to lava effusion) and subsequent vulcanian explosions, the Shinmoedake crater experienced intermittent eruptions in 2018. The May 14, 2018 eruption began at 14:44 with a vulcanian eruption, with the eruption plume rising 4500 m above the crater rim. Thereafter, it transitioned to an ash eruption; the plume height decreased gradually until the eruption ceased at 16:10. The tephra fall deposits were distributed more than 27 km to the southeast of the source crater; the mass of the tephra fall deposit was approximately 2.1 × 107 kg, calculated based on an isomass map. The deposit incidence differed between the east and west sides of the major dispersal axis. The deposits found east of the main dispersal axis were primarily composed of coarse to medium sand-sized particles with no fine fraction (fine sand to silt in size). In contrast, the deposits west of the axis were finer-grained than those east of the axis. We analyzed photographs of the eruption plume, along with the regional meteorological data and the dispersal and grain-size characteristics of the deposits, and reached the following conclusion: during the May 14, 2018 eruption, the wind directions above the Shinmoedake crater fluctuated across altitudes. The westerly winds dispersed the eruption plume that rose to a higher altitude, containing coarser tephra associated with the initial vulcanian eruption, further to the east rather than along the main axis. In contrast, a lower-altitude ash eruption plume that was rich in fine materials was dispersed westward rather than along the main axis, which was influenced by northerly winds. The findings of this study can support the analysis of similar volcanic events.

Graphical Abstract
Revascularization with BYCROSS atherectomy device- protocol of a prospective multicenter observational study
Authors: Liebetrau Dominik , Teßarek Joerg , Elger Florian , Zerwes Sebastian , Peters Viktoria , Scheurig-Münkler Christian , Hyhlik-Dürr Alexander
Published: December 2023

Background

The BYCROSS™ device is a novel device intended for use in atherectomy of the peripheral arterial disease (PAD). With the BYCROSS™ atherectomy system, also prolonged calcifying lesions can be treated in a minimally invasive manner, which was previously reserved for bypass surgery. The aim of this study is to collect additional clinical data on safety and performance of the BYCROSS™ from patients undergoing revascularization of severely stenotic or occluded peripheral arterial vessels with the BYCROSS™.

Methods and design

This is an investigator-initiated national prospective multicenter observational study in patients with PAD. Sixty patients (20 per center) with PAD with stenosis higher than 80% or complete occlusion (de novo or recurrent stenosis) of vessels below the aortic bifurcation (min 3 mm vessel diameter) will be recruited. Three vascular surgery centers are participating in the study. The primary efficacy endpoint is procedural success, defined as passage of the occlusion through the BYCROSS device, and safety outcomes, explicated as freedom from device-related serious adverse events (SADEs). Secondary endpoints include primary and secondary patency rates, change in Rutherford classification, and freedom from amputation at 3 and 12 months.

Discussion

The BYCROSS atherectomy system may be a novel device for the minimally invasive treatment of prolonged calcified lesions previously reserved for bypass surgery. This national prospective multicenter observational study could represent another step in demonstrating the efficancy and safety of this device for treatment of PAD.

Trial registration

#DRKS00029947 (who.int).

Protocol approval id

#22–0047(Ethics Committee at Ludwig-Maximilians-University Munich).
Role of Montelukast in modulation of response to sepsis in preterm infants: a randomized-controlled trial
Authors: El-Shehaby Nouran , El-Shahawy Heba Abdelhameed , Nasef Nehad , El-Sallab Shadia , EL-Halaby Hanan
Published: December 2023

Background

Since inflammatory mediators play a crucial role in the pathophysiology of neonatal sepsis. Montelukast, as an anti-inflammatory drug, could be a beneficial therapy. In searching the literature, no previous research addressed the role of Montelukast in neonatal sepsis; hence, this study aimed to explore the adjuvant role of Montelukast in regulating the inflammatory response associated with neonatal sepsis and its associated effect on the clinical outcomes.

Methods

An open-label, randomized controlled intervention trial conducted on 40 late preterm newborn infants (gestational age 340/7 to 366/7 weeks) admitted to NICU, with clinical evidence of sepsis. In the Montelukast group (n = 20), infants received oral Montelukast once daily for 10 days (infant's weight < 2 kg received 1.5 mg whereas > 2 kg received 2 mg) with antibiotics plus routine supportive care. In the routine care group (n = 20), infants received antibiotics plus routine supportive care. Primary outcome was the serum level of tumor necrosis factor (TNF) alpha at day 10 of therapy. Secondary clinical and laboratory outcomes were reported along hospital admission.

Results

Baseline characteristics were non-significantly different between both groups. After 10 days of therapy, TNF alpha level was significantly lower in the Montelukast group (80.73 ± 50.25 versus 119.54 ± 58.46; p = 0.03). There were non-significant differences between both groups regarding duration of NICU admission, antibiotics duration or modalities and duration of respiratory support. C-reactive protein didn’t differ between both groups (p = 0.256). No documented significant adverse effects of Montelukast during the study period.

Conclusions

In late preterm neonates with sepsis, 10 days of Montelukast therapy as an adjuvant to antibiotics lowered TNF alpha level without any impact on clinical outcomes.

Trial registration

The study was approved by Mansoura Faculty of Medicine institutional research board (IRB) (MS/17.06.95) and it was registered in clinical trials database (clinicaltrials.gov, ID: NCT04474327; registered July 16, 2020).
DNA methylation in hearing-related genes in non-syndromic sensorineural hearing loss patients
Authors: Eğilmez Oğuz Kadir , Can Sermet , Kalcıoğlu M. Tayyar , Tan Berna Demircan , Yılmaz Sarenur , Yiğit Özgür , Durna Muhammed Yusuf , Akdeniz Esra , Akalin Ibrahim
Published: December 2023

Background

Our understanding of epigenetic modifications in the inner ear is very limited. Although epigenetic regulation of genes related to individual organ- and system-limited pathologies are generally expected to be tissue-specific, DNA methylation patterns in peripheral blood (PB) are found to be associated with the presence of several diseases with no typical hematological involvement. Here, we aimed to investigate whether there is a correlation between hearing-related genes’ promoter region methylation in the PB samples with the presence of non-syndromic sensorineural hearing loss (NSSHL) with an aim of future utilization of DNA methylation as biomarkers in hearing loss. The study included 26 patients with NSSHL and a control group of 20 healthy individuals. CpG islands in the promoter regions of the GJB-2, GJB-6, and SLC24A genes were analyzed using bisulfite sequencing, and methylation percentages were analyzed.

Results

Methylation levels at the 1st region of GJB-6 and the 1st and the 4th regions of SLC26A4 were found to differ significantly (p = 0.039, p = 0.042, and p = 0.029, respectively) between the patients and the control group. There was no statistically significant difference in methylation percentages of GJB-2 promoters. We also found that parents’ consanguinity determines the methylation levels in patients’ families.

Conclusions

According to our knowledge, this is the first study that investigates epigenetic changes in the PB of patients with NSSHL. Despite the small sample size, our findings indicate that DNA methylation patterns in the PB could be of use for understanding epigenetic changes in the inner ear and the clinical management of NSSHL.
HLA Haplotypes and Relapse After Hematopoietic Cell Transplantation
Authors: Petersdorf Effie W. , McKallor Caroline , Malkki Mari , He Meilun , Spellman Stephen R. , Gooley Theodore , Stevenson Philip
Published: December 2023

PURPOSE

Recurrence of blood malignancy is the major cause of hematopoietic cell transplant failure. HLA class II molecules play a fundamental role in antitumor responses but the role of class II haplotypes is not known.

METHODS

HLA-DR, -DQ, -DM, and -DO allele variation was determined in 1,629 related haploidentical transplants to study the clinical significance of individual molecules and haplotypes.

RESULTS

Outcome correlated with patient and donor variation for HLA-DRβ residue 86 (Gly/Val), HLA-DQ (G1/G2) heterodimers, and donor HLA-DM (DM11,11/nonDM11,11) molecules, and depended on patient-donor mismatching. Risks of relapse were lower for DRβ-86 GlyGly patients when the donor was GlyVal (hazard ratio [HR], 0.46 [95% CI, 0.30 to 0.68]; P < .001); GlyVal patients benefited from HLA-DRB1–matched donors, whereas no donor was superior to another for ValVal patients. G1G2 patients with G1G2-mismatched donors had lower relapse. Transplantation from donors with DMα residue 184 ArgHis was associated with higher risk of relapse (HR, 1.60 [95% CI, 1.09 to 2.36]; P = .02) relative to ArgArg. Relapse and mortality risks differed across HLA-DR-DQ-DM haplotypes.

CONCLUSION

HLA class II haplotypes may be functional constituents of the transplantation barrier, and their consideration in patients and donors may improve the success of transplantation.
A Population Model of Time-Dependent Changes in Serum Creatinine in (Near)term Neonates with Hypoxic-Ischemic Encephalopathy During and After Therapeutic Hypothermia
Authors: Krzyzanski Wojciech , Wintermark Pia , Annaert Pieter , Groenendaal Floris , Şahin Suzan , Öncel Mehmet Yekta , Armangil Didem , Koc Esin , Battin Malcolm R. , Gunn Alistair J. , Frymoyer Adam , Chock Valerie Y.-L. , Keles Elif , Mekahli Djalila , van den Anker John , Smits Anne , Allegaert Karel
Published: December 2023

The objective was to apply a population model to describe the time course and variability of serum creatinine (sCr) in (near)term neonates with moderate to severe encephalopathy during and after therapeutic hypothermia (TH). The data consisted of sCr observations up to 10 days of postnatal age in neonates who underwent TH during the first 3 days after birth. Available covariates were birth weight (BWT), gestational age (GA), survival, and acute kidney injury (AKI). A previously published population model of sCr kinetics in neonates served as the base model. This model predicted not only sCr but also the glomerular filtration rate normalized by its value at birth (GFR/GFR0). The model was used to compare the TH neonates with a reference full term non-asphyxiated population of neonates. The estimates of the model parameters had good precision and showed high between subject variability. AKI influenced most of the estimated parameters denoting a strong impact on sCr kinetics and GFR. BWT and GA were not significant covariates. TH transiently increased $$\mathrm{sCr}$$
sCr
in TH neonates over the first days compared to the reference group. Asphyxia impacted not only GFR, but also the $$\mathrm{sCr}$$
sCr
synthesis rate. We also observed that AKI neonates exhibit a delayed onset of postnatal GFR increase and have a higher $$\mathrm{sCr}$$
sCr
synthesis rate compared to no-AKI patients. Our findings show that the use of $$\mathrm{sCr}$$
sCr
as marker of renal function in asphyxiated neonates treated with TH to guide dose selection for renally cleared drugs is challenging, while we captured the postnatal sCr patterns in this specific population.

Graphical Abstract
Investigating a method for macroscale energy extraction from random electrons movement
Authors: Peivandi M. , Kouhikamali R.
Published: December 2023

This paper aims to investigate a novel method for regularizing the random movements of electrons, in order to generate net movement and extract energy from the resulting electromotive force. The proposed method involves designing anisotropic conditions, focusing on exploring the effects of surface roughness on a metal wire in a two-dimensional space with the presence of a magnetic field. This paper presents a mathematical model for studying the proposed method. Furthermore, simulation results are analyzed and discussed in the context of the proposed method. By investigating the effects of surface roughness on electrons movement and voltage generation, this paper aims to contribute to the development of new methods for energy extraction from random electrons movement.
Melanin-Concentrating Hormone Is Associated With Delayed Neurocognitive Recovery in Older Adult Patients With Preoperative Sleep Disorders Undergoing Spinal Anesthesia
Authors: Gao Yi , Zhou Qi , Li Haibo , Zhao Yunjiao , Zhu Hongyan , Zhang Xizhe , Li Yun
Published: December 2023

BACKGROUND:

Aging and preoperative sleep disorders are the main risk factors affecting postoperative cognitive outcomes. However, the pathogenesis of delayed neurocognitive recovery after surgery remains ambiguous, and there is still a lack of potential biomarkers for delayed neurocognitive recovery in older adult patients with preoperative sleep disorders. Our study aimed to explore the relationship between melanin-concentrating hormone (MCH) and delayed neurocognitive recovery early after surgery in older adult patients with preoperative sleep disorders.

METHODS:

In this monocentric prospective observational study, 156 older adult patients (aged 65 years or older) with preoperative sleep disorders undergoing elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) were included at an academic medical center in Inner Mongolia, China, from October 2021 to November 2022, and all patients underwent spinal anesthesia. The Pittsburgh Sleep Quality Index (PSQI) was applied to assess the preoperative sleep quality of all patients, and preoperative sleep disorders were defined as a score of PSQI >5. We measured the levels of cerebrospinal fluid (CSF) MCH and plasma MCH of all patients. The primary outcome was delayed neurocognitive recovery early after surgery. All patients received cognitive function assessment through the Montreal Cognitive Assessment (MoCA) 1 day before and 7 days after surgery (postoperative day 7 [POD7]). Delayed neurocognitive recovery was defined as a score of POD7 MoCA <26. The potential confounders included variables with P < .2 in the univariate logistic analysis, as well as the important risk factors of delayed neurocognitive recovery reported in the literature. Multivariable logistic regression model based on the Enter method assessed the association of MCH and delayed neurocognitive recovery in older adult patients with preoperative sleep disorders.

RESULTS:

Fifty-nine (37.8%) older adult patients with preoperative sleep disorders experienced delayed neurocognitive recovery at POD7. Increase in CSF MCH levels (odds ratio [OR] for an increase of 1 pg/mL = 1.16, 95% confidence interval [CI], 1.09–1.23, P < .001) and decrease in plasma MCH levels (OR for an increase of 1 pg/mL = 0.92, 95% CI, 0.86–0.98, P = .003) were associated with delayed neurocognitive recovery, after adjusting for age, sex, education, baseline MoCA scores, American Society of Anesthesiologists (ASA) grade, and coronary heart disease (CHD).

CONCLUSIONS:

In older adult patients with preoperative sleep disorders, MCH is associated with the occurrence of delayed neurocognitive recovery after surgery. Preoperative testing of CSF MCH or plasma MCH may increase the likelihood of identifying the high-risk population for delayed neurocognitive recovery in older adult patients with preoperative sleep disorders.