bluuebunny/crossref_metadata_2025 huggingface dataset:
Salidroside attenuates HALI via IL-17A-mediated ferroptosis of alveolar epithelial cells by regulating Act1-TRAF6-p38 MAPK pathway
Authors: Guo Baoyue , Zuo Zhongfu , Di Xingwei , Huang Ying , Gong Gu , Xu Bo , Wang Lulu , Zhang Xiaoyu , Liang Zhuang , Hou Yang , Liu Xuezheng , Hu Zhansheng
Published: November 2022

Background and Purpose

Hyperoxia-induced acute lung injury (HALI) is a critical life-threatening disorder characterized by severe infiltration immune cells and death of type II alveolar epithelial cells (AECII). However, little is known about the relations between immune cells and AECII in HALI. IL-17A is a pro-inflammatory cytokine mainly secreted by Th17 cells, contributing to the pathogenesis of various inflammatory diseases. The present study investigated the role of IL-17A in cell–cell communication between immune cells and AECII in HALI, and explored the therapeutic effect of salidroside (Sal, a natural anti-inflammatory agents) on HALI.

Methods

Mice with HALI were induced by exposure to hyperoxia over 90% for 12 h, 24 h, 48 h or 72 h, and the optimal timing was detected by H&E and Masson staining. Ferroptosis was confirmed by detecting the levels of MDA, Fe2+ and GPX4, and the morphological alterations of AECII under transmission electron microscopy. The expression of pro-inflammatory cytokine, including IL-6, TGF-β1, IL-17A and IL-17A receptor (IL-17RA) were measured by Western blotting and immunohistochemical stanning. The ferroptosis-related Act1/TRAF6/p38 MAPK pathway was detected by Western blotting. The role of pro-inflammatory cytokine IL-17A for AECII ferroptosis, and the effect of Sal on HALI were investigated by administration of Y-320 (IL-17 inhibitor) and Sal respectively 3 days before mice exposed to hyperoxia.

Results

Mice exposed to hyperoxia for 24 h suffered sufficient HALI with inflammatory cell infiltration and collagen deposition, and exhibited features of ferroptosis under TME. Meanwhile, compared with sham mice, mice exposed to hyperoxia showed down-regulation of GPX4, and up-regulation of IL-6, TGF-β1, IL-17A, IL-17RA, Act1, TRAF6, p38 MAPK and p-p38 MAPK. Moreover, inhibition of IL-17A with Y-320 or administration with Sal could reverse the effect caused by hyperoxia respectively.

Conclusions

IL-17A is associated with immune cells infiltration in HALI, and contributes to ferroptosis of AECII that related to Act1/TRAF6/p38 MAPK pathway. Additionally, Sal protects against HALI throughout the whole pathogenic process.
OTUD4-mediated GSDME deubiquitination enhances radiosensitivity in nasopharyngeal carcinoma by inducing pyroptosis
Authors: Di Muping , Miao Jingjing , Pan Qiuzhong , Wu Zonglong , Chen Boyu , Wang Muru , Zhao Jingjing , Huang Huageng , Bai Jiewen , Wang Qijing , Tang Yan , Li Yongqiang , He Jia , Xiang Tong , Weng Desheng , Wang Lin , Xia Jianchuan , Zhao Chong
Published: November 2022

Background

Radioresistance is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure. Previous studies have focused on the deficits in cellular apoptosis as a mechanism for radioresistance; however, additional potential death modes involved in modulating radiosensitivity of NPC have not been explored.

Methods

Pyroptosis was assessed by phase-contrast imaging, LDH release assays, live cell imaging, and Western blotting. In vitro and in vivo assays were used to investigate the function of gasdermin E (GSDME) and ovarian tumor family deubiquitinase 4 (OTUD4). NPC tissues were analyzed using Western blotting, immunohistochemistry, and real-time PCR. The molecular mechanism was determined using immunoprecipitation assays and mass spectrometry.

Results

Live cell imaging revealed that 40—75% of irradiation-induced dead NPC cells were pyroptotic cells. Furthermore, irradiation-induced pyroptosis is triggered by GSDME, which are cleaved by activated caspase-3 in the intrinsic mitochondrial pathway. Additionally, GSDME was significantly downregulated in radioresistant NPC specimens. Low GSDME expression was a predictor of worse prognosis and conferred NPC radioresistance both in vitro and in vivo. Mechanistically, OTUD4 deubiquitinated and stabilized GSDME, enhancing radiosensitivity of NPC cells by promoting pyroptosis. Clinically, OTUD4 was significantly correlated with GSDME in NPC biopsies, and patients with low expression of both OTUD4 and GSDME suffered the worst radiotherapy response and survival.

Conclusions

GSDME-dependent pyroptosis is a critical determinant of radiosensitivity in NPC, and is modulated by OTUD4 via deubiquitinating and stabilizing GSDME. These findings reveal a promising novel direction to investigate radioresistance and suggest potential therapeutic targets for sensitizing NPC to radiotherapy.
Microglia and metastases to the central nervous system: victim, ravager, or something else?
Authors: Caffarel Maria M. , Braza Mounia S.
Published: November 2022

Central nervous system (CNS) metastases are a major cause of death in patients with cancer. Tumor cells must survive during their migration and dissemination in various sites and niches. The brain is considered an immunological sanctuary site, and thus the safest place for metastasis establishment. The risk of brain metastases is highest in patients with melanoma, lung, or breast cancers. In the CNS, metastatic cancer cells exploit the activity of different non-tumoral cell types in the brain microenvironment to create a new niche and to support their proliferation and survival. Among these cells, microglia (the brain resident macrophages) display an exceptional role in immune surveillance and tumor clearance. However, upon recruitment to the metastatic site, depending on the microenvironment context and disease conditions, microglia might be turned into tumor-supportive or -unsupportive cells. Recent single-cell ‘omic’ analyses have contributed to clarify microglia functional and spatial heterogeneity during tumor development and metastasis formation in the CNS. This review summarizes findings on microglia heterogeneity from classical studies to the new single-cell omics. We discuss i) how microglia interact with metastatic cancer cells in the unique brain tumor microenvironment; ii) the microglia classical M1-M2 binary concept and its limitations; and iii) single-cell omic findings that help to understand human and mouse microglia heterogeneity (core sensomes) and to describe the multi-context-dependent microglia functions in metastases to the CNS. We then propose ways to exploit microglia plasticity for brain metastasis treatment depending on the microenvironment profile.
Infantile Pompe disease with intrauterine onset: a case report and literature review
Authors: Xi Hongmin , Li Xianghong , Ma Lili , Yin Xiangyun , Yang Ping , Zhang Lulu
Published: November 2022

Background

Pompe disease is a rare autosomal recessive disease. Acid alpha−glucosidase (GAA) deficiency leads to glycogen storage in lysosomes, causing skeletal, cardiac, and smooth muscle lesions. Pompe disease is progressive, and its severity depends on the age of onset. Classic infantile Pompe disease, the most severe form, is characterized by an age of onset before 12 months. Pompe disease with intrauterine onset has rarely been reported.

Case presentation

The proband was born at a gestational age of 40 weeks and 3 days and admitted to our hospital because of intrauterine cardiac hypertrophy, shortness of breath, and cyanosis until 13 min postnatally. Physical examination at admission revealed poor responsiveness, pale skin, shortness of breath, reduced limb muscle tone, and bilateral pedal edema. The heart sounds were weak, and no heart murmur was heard. Echocardiography showed left (9 mm) and right (5 mm) ventricular hypertrophies. The patient was subjected to non−invasive ventilator−assisted respiration, fluid restriction, diuresis, and metoprolol treatment. Infantile Pompe disease was diagnosed on day 16 with a GAA enzymatic activity of 0.31 µmol/L/h and with the full−penetrance genetic test showing the homozygous gene mutation c.1844G>T(p.Gly615Val). Enzyme replacement therapy was refused by the patient’s parents, and the patient died at seven months of age from cardiopulmonary failure.

Conclusion

Infants with intrauterine−onset Pompe disease usually have early manifestations of heart disease. Prompt GAA enzymatic activity determination and molecular genetic testing are helpful in aiding the parents’ decision and planning the treatment.
Production of lactic acid from pasta wastes using a biorefinery approach
Authors: Marzo-Gago Cristina , Venus Joachim , López-Gómez José Pablo
Published: November 2022

A total of 398 kt of pasta waste (PW), generated during the production process of pasta, were produced in 2021. Due to its chemical composition and practically zero cost, PW has already been studied as a raw material for the production of lactic acid (LA) through fermentations. The main objective of this article was to improve the economic viability of the process by replacing commercial enzymes, necessary for starch hydrolysis in PW, with raw enzymes also produced from wastes. Enzyme synthesis was achieved through solid-state fermentation (SsF) of wheat bran by Aspergillus awamori or Aspergillus oryzae at various moisture contents. The maximum amylase activity (52 U/g dry solid) was achieved after 2 days of fermentation with A. awamori at 60% of moisture content. After that, the enzymes were used to hydrolyse PW, reaching 76 g/L of total sugars, 65 g/L of glucose and a yield of 0.72 gglu/gds with the enzymes produced by A. awamori. Subsequently, the hydrolysate was fermented into LA using Bacillus coagulans A559, yielding 52 g/L and 49 g/L with and without yeast extract, respectively. Remarkably, compared to the process with commercial enzymes, a higher LA yield was reached when enzymes produced by SsF were added (0.80 gLA/gglu). Furthermore, the productivities between the two processes were similar (around 3.9 g/L/h) which highlights that yeast extract is not necessary when using enzymes produced by SsF.
Osteolytic metatarsal osteomyelitis regenerated by combined treatment of artificial carbon dioxide foot bathing and povidone–iodine sugar ointment: a case report
Authors: Hihara Masakatsu , Fukui Michika , Mitsui Toshihito , Kakudo Natsuko , Kuro Atsuyuki
Published: November 2022

Background

In recent years, the number of patients with ischemic skin ulcers due to diabetes mellitus and arteriosclerosis obliterans are increasing. Accordingly, endovascular therapy, drugs, and various wound dressings have been developed and applied to diabetic foot ulcers, and negative-pressure wound therapy, which often requires expensive and burdensome procedures for medical personnel, has also become popular. So simple and minimal invasive home treatment by the patient or their caregiver is required.

Case presentation

The present patient (77 years old, male, Asian) had developed left sole ulcers with draining pus that were resistant to conventional treatment, and he suffered from gait disturbance. We report a case of metatarsal osteomyelitis in a patient with diabetes mellitus and arteriosclerosis obliterans, in whom artificial carbon dioxide foot bathing and povidone–iodine sugar ointment were used continuously to promote bone and joint regeneration, and skin ulcer healing.

Conclusions

A simple therapeutic intervention with artificial carbon dioxide foot bathing and povidone–iodine sugar ointment can improve not only ischemic skin ulcers, but also the bone and joint regeneration of ischemic limbs. This therapy can lead to a reduction in healthcare costs for a huge number of diabetic patients.
Cerebrolysin induces hair repigmentation associated to MART-1/Melan-A reactivation
Authors: Villarreal-Reyna Gustavo , Garza-Morales Rodolfo , Soto-Domínguez Adolfo , Montañez-Guerrero Lorena , Saucedo-Cárdenas Odila , Gómez-Flores Minerva , Ocampo-Garza Jorge Alejandro , Pérez-Trujillo José Juan , Montes-de-Oca-Luna Roberto
Published: November 2022

Hair graying, a prototypical sign of human aging, is a progressive loss of pigmentation from growing hair shafts caused by disease and as a side effect of medications. Cerebrolysin is a neuropeptide preparation that mimics the effect of endogenous neurotrophic factors. Cerebrolysin has been widely used in neurologic conditions, such as cerebral stroke, Alzheimer’s disease, and dementia, among others. Cerebrolysin treatment has achieved to regain or maintain the cognitive ability of affected patients; however, up to date, there are no reports about the reactivation of hair pigmentation. We describe a previously not described effect occurring on patients receiving Cerebrolysin treatment for neurologic diseases and whether this effect is associated in reactivation of melanocytes and melanin expression. Here, we report five patients (mean age, 70.6 years), who also had age-related hair graying and scalp hair repigmentation during Cerebrolysin treatment. Macroscopic analysis revealed hair repigmentation consisted in diffuse darkening of the scalp hair. Impregnation and immunostaining analysis were performed on scalp biopsies taken before and after Cerebrolysin treatment; the results showed greater melanin and melanocyte marker MART-1/Melan-A staining following Cerebrolysin treatment. We present, to our knowledge, the first report on hair repigmentation is a previously not described effect occurring following Cerebrolysin treatment.
Phenomenological support for escape theory: a qualitative study using explicitation interviews with emotional eaters
Authors: Shireen Huma , Castelli Samantha , Legault Maurice , Dor-Ziderman Yair , Milad Julia , Knäuper Bärbel
Published: November 2022

The current study explored the phenomenology of emotional eating, that is, the descriptive knowledge of what one perceives, senses, and knows in one's immediate awareness and experience during emotional eating. Eight individuals with emotional eating were interviewed twice using explicitation interviewing. Data were analyzed using thematic analysis, which resulted in nine themes describing the diachronic (or temporal) unfolding of emotional eating and several sub-themes that described various synchronic (or experiential) dimensions of this unfolding. The core findings of this study support the escape theory of emotional eating and recommend future directions to investigate the self-related shifts proposed by this theory. Namely, the findings show that individuals tend to use food to regulate their emotions by reducing the unpleasant experience of negative emotions and the associated unpleasant narrative processing or ruminations about stressors that caused the negative emotions. This then leads to an urge to eat associated with a desire for the sensory experience of eating. Eating then enables individuals to reduce thoughts about their stressors and bring themselves into the present moment through embodiment. Future quantitative research could investigate this mechanism of shifting from narrative to embodied processing to regulate emotions in emotional eating to develop treatment programs, such as mindfulness-based programs, that could encourage such a shift and emotion regulation without the use of food.
Initial psychometric properties of an Arabic version of the disordered eating attitudes in pregnancy scale (A-DEAPS) among Lebanese pregnant women
Authors: Gerges Sarah , Obeid Sahar , Hallit Souheil
Published: November 2022

Background

Pregorexia refers to the excessive fear of pregnancy-induced weight gain and the drive to control it through various measures (e.g., extreme restriction of calorie intake, excessive exercising, or diuretics and/or laxatives consumption). The Disordered Eating Attitudes in Pregnancy Scale (DEAPS, Bannatyne et al., in: Disordered eating in pregnancy: the development and validation of a pregnancy-specific screening instrument. Bond University, 2018) is a brief pregnancy-specific instrument developed to screen for antenatal eating disorders. Our study’s objective was to examine the reliability and psychometric properties of the Arabic version of this pregnancy-specific scale among Lebanese pregnant women.

Methods

We conceived and implemented a cross-sectional survey between June and July 2021 (N = 433). The sample was randomly divided in two as per the SPSS data selection option; the first subsample was used to conduct the DEAPS items’ exploratory factor analysis (EFA), whereas the second was used for the confirmatory factor analysis (CFA). Within this study, we described multiple indices of goodness-of-fit: the Relative Chi-square (χ2/df), Root Mean Square Error of Approximation (RMSEA), Tucker Lewis Index (TLI), and Comparative Fit Index (CFI).

Results

An EFA was conducted on subsample 1 (N = 207), chosen randomly from the original sample. With the exception of item 8, all other 13 items converged over a two-factor solution [Factor 1 (3 items): Body Image Concerns during Pregnancy, and Factor 2 (10 items): Disordered Eating Attitudes during Pregnancy]. In subsample 2 (N = 226), the CFA results showed that the one-factor model (Factor 2: 10 items), which derived from the EFA conducted on subsample 1, fitted well accordingly to CFI, TLI, and χ2/df values, and fitted modestly according to RMSEA. The CFA estimates obtained for model 1 (original scale of 14 items) and model 2 (according to the two-factor solution obtained from the EFA in subsample 1) fitted less than the third model (Factor 2). The analysis thus suggested retaining only Factor 2 with 10 items in the Arabic version of the scale.

Conclusion

Our study was able to provide preliminary evidence that the Arabic 10-item version of the DEAPS seems to be a good and reliable tool for the assessment of disordered eating attitudes among Lebanese pregnant women.
Accuracy and stability of computer-aided customized lingual fixed retainer: a pilot study
Authors: Kang Seung-Hyun , Kwon Jae-Sung , Chung Chooryung Judi , Cha Jung-Yul , Lee Kee-Joon
Published: November 2022

Background

With advances in digital technology, new types of lingual fixed retainers are being developed. However, there are few studies that quantitatively evaluate the accuracy and stability of lingual fixed retainers. The aim of this study was to assess the accuracy and stability of two types of computer-aided customized lingual fixed retainers and a conventional lingual fixed retainer.

Methods

A total of 10 maxillary and 10 mandibular duplicated dental models were selected, and then, three types of retainers were fabricated on the canine-to-canine area for each model. To evaluate accuracy, wire clearance at interproximal area (WCI) was measured using superimposition analysis. Initial flatness deformation was also measured for vertical distortion of retainers. Lateral width, anteroposterior length, and flatness deformation were measured at three-time points for stability assessment. Thermocycling was used to induce 6 months of time flow.

Results

The custom-bent group showed significantly higher WCI than the custom-cut and manual groups in the maxillary arch (P = 0.002). The custom-cut group showed significantly less flatness deformation, which was followed by the custom-bent and manual groups in both the maxillary and mandibular arch (P < 0.001). There was no significant difference in stability between the three retainer groups during 5100 cycles of thermocycling (corresponding to 6-month period).

Conclusions

Since there was no difference in stability between the three groups, it is recommended to use custom-cut type retainers in light of accuracy. However, accuracy and stability are not the only factors to consider when selecting type of retainers. Because each retainer has advantages and disadvantages, the type of retainers should be decided in consideration of the clinical environment.
Using country-specific Q-matrices for cognitive diagnostic assessments with international large-scale data
Authors: Delafontaine Jolien , Chen Changsheng , Park Jung Yeon , Van den Noortgate Wim
Published: November 2022

In cognitive diagnosis assessment (CDA), the impact of misspecified item-attribute relations (or “Q-matrix”) designed by subject-matter experts has been a great challenge to real-world applications. This study examined parameter estimation of the CDA with the expert-designed Q-matrix and two refined Q-matrices for international large-scale data. Specifically, the G-DINA model was used to analyze TIMSS data for Grade 8 for five selected countries separately; and the need of a refined Q-matrix specific to the country was investigated. The results suggested that the two refined Q-matrices fitted the data better than the expert-designed Q-matrix, and the stepwise validation method performed better than the nonparametric classification method, resulting in a substantively different classification of students in attribute mastery patterns and different item parameter estimates. The results confirmed that the use of country-specific Q-matrices based on the G-DINA model led to a better fit compared to a universal expert-designed Q-matrix.
Health system preparedness in infectious diseases: perspective of Malaysia, a middle-income country, in the face of monkeypox outbreaks
Authors: Tao Chang Chee , Lim Xin-Jie , Amer Nordin Awatef , Thum Chern Choong , Sararaks Sondi , Periasamy Kalaiarasu , Rajan Philip
Published: November 2022

The World Health Organization declared monkeypox as a Public Health Emergency of International Concern on July 23, 2022. As of July 25th, 2022, there were 16,016 laboratory-confirmed cases reported worldwide with 5 deaths. Malaysia's Health Ministry has developed a five-point strategy to prepare for the impending threat of the infectious disease, encompassing early detection of monkeypox, consolidation of laboratory diagnostic facilities, case management and treatment, cluster management, and strengthening public awareness. Crisis and disaster preparedness within a nation's health system is paramount to preventing disease spread. Various strategies for developing resilience in the face of global infectious disease spread were discussed. The current disease preparedness and response framework and guidelines in Malaysia have established a health system that is proactive and responsive to any potential infectious disease outbreaks. Despite this, the future remains unpredictable, and ongoing fortification is required as events unfold.
Side matters: differences in functional outcome and quality of life after thrombectomy in left and right hemispheric stroke
Authors: Deb-Chatterji Milani , Flottmann Fabian , Meyer Lukas , Brekenfeld Caspar , Fiehler Jens , Gerloff Christian , Thomalla Götz ,   the GSR-ET-Investigators, Gerloff C. , Fiehler J. , Thomalla G. , Alegiani A. , Boeckh-Behrens  , Wunderlich Silke , Ernemann Ulrike , Poli Sven , Siebert Eberhard , Nolte Christian H. , Zweynert Sarah , Bohner Georg , Ludolph Alexander , Henn Karl-Heinz , Schäfer Jan Hendrik , Keil Fee , Röther Joachim , Eckert Bernd , Berrouschot Jörg , Bormann Albrecht , Dorn Franziska , Petzold Gabor , Kraemer Christoffer , Leischner Hannes , Trumm Christoph , Tiedt Steffen , Kellert Lars , Petersen Martina , Stögbauer Florian , Braun Michael , Hamann Gerhard F. , Gröschel Klaus , Uphaus Timo , Reich Arno , Nikoubashman Omid , Schellinger Peter , Borggrefe Jan , Hattingen Jörg , Liman Jan , Ernst Marielle
Published: November 2022

Background

Patients with a left (LHS) or right hemispheric stroke (RHS) differ in terms of clinical symptoms due to lateralization of specific cortical functions. Studies on functional outcome after stroke and endovascular thrombectomy (EVT) comparing both hemispheres showed conflicting results so far. The impact of stroke laterality on patient-reported health-related quality of life (HRQoL) after EVT has not yet been adequately addressed and still remains unclear.

Methods

Consecutive stroke thrombectomy patients, derived from a multi-center, prospective registry (German Stroke Registry) between June 2015 and December 2019, were included in this study. At 90 days, outcome after EVT was assessed by the modified Rankin scale (mRS) and HRQoL using the European QoL-five dimensions questionnaire utility-index (EQ-5D-I; higher values indicate better HRQoL) in patients with LHS and RHS. Adjusted regression analysis was applied to evaluate the influence of stroke laterality on outcome after EVT.

Results

In total, 5683 patients were analyzed. Of these, 2953 patients (52.8%) had LHS and 2637 (47.2%) RHS. LHS patients had a higher baseline NIHSS (16 vs. 13, p < 0.001) and a higher ASPECTS (9 vs. 8, p < 0.001) compared to RHS patients. Among survivors, patients with LHS less frequently had a self-reported affected mobility (p = 0.037), suffered less often from pain (p = 0.04) and anxiety/depression (p = 0.032) three months after EVT. After adjusting for confounders (age, sex, baseline NIHSS), LHS was associated with a better HRQoL (ß coefficient 0.04, CI 95% 0.017–0.063; p = 0.001), and better functional outcome assessed by lower values on the mRS (ß coefficient − 0.109, CI 95% − 0.217–0.000; p = 0.049).

Conclusions

Ninety days after EVT, LHS patients have a better functional outcome and HRQoL. Patients with RHS should be actively assessed and treated for pain, anxiety and depression to improve their HRQoL after EVT.
Cobimetinib Plus Vemurafenib in Patients With Colorectal Cancer WithBRAFMutations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study
Authors: Klute Kelsey A. , Rothe Michael , Garrett-Mayer Elizabeth , Mangat Pam K. , Nazemzadeh Reza , Yost Kathleen J. , Duvivier Herbert L. , Ahn Eugene R. , Cannon Timothy L. , Alese Olatunji B. , Krauss John C. , Thota Ramya , Calfa Carmen J. , Denlinger Crystal S. , O'Lone Raegan , Halabi Susan , Grantham Gina N. , Schilsky Richard L.
Published: November 2022

PURPOSE

TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. The results of a cohort of patients with colorectal cancer (CRC) with BRAF mutations treated with cobimetinib (C) plus vemurafenib (V) are reported.

METHODS

Eligible patients had advanced CRC, no standard treatment options, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with BRAF V600E/D/K/R mutations, and no MAP2K1/2, MEK1/2, or NRAS mutations. C was taken 60 mg orally once daily for 21 days followed by seven days off, and V was taken 960 mg orally twice daily. Simon's two-stage design was used with a primary study end point of objective response or stable disease of at least 16 weeks duration. Secondary end points were progression-free survival, overall survival, and safety.

RESULTS

Thirty patients were enrolled from August 2016 to August 2018; all had CRC with a BRAF V600E mutation except one patient with a BRAF K601E mutation. Three patients were not evaluable for efficacy. Eight patients with partial responses and six patients with stable disease of at least 16 weeks duration were observed for disease control and objective response rates of 52% (95% CI, 35 to 65) and 30% (95% CI, 14 to 50), respectively. The null hypothesis of 15% disease control rate was rejected ( P < .0001). Thirteen patients had at least one grade 3 adverse event or serious adverse event at least possibly related to C + V: anemia, decreased lymphocytes, dyspnea, diarrhea, elevated liver enzymes, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, and upper gastrointestinal hemorrhage.

CONCLUSION

The combination of C + V has antitumor activity in heavily pretreated patients with CRC with BRAF mutations.
Circulating miRNAs Respond to Denosumab Treatment After 2 Years in Postmenopausal Women With Osteoporosis—the MiDeTe study
Authors: Messner Zora , Carro Vázquez David , Haschka Judith , Grillari Johannes , Resch Heinrich , Muschitz Christian , Pietschmann Peter , Zwerina Jochen , Hackl Matthias , Kocijan Roland
Published: November 2022

Context

MicroRNAs (miRNAs)—short, single-stranded, noncoding RNAs—regulate several biological processes, including bone metabolism.

Objective

We investigated circulating miRNAs as promising biomarkers for treatment monitoring in women with postmenopausal osteoporosis on denosumab (DMAB) therapy.

Methods

In this prospective, observational, single-center study, 21 postmenopausal women treated with DMAB were included for a longitudinal follow-up of 2 years. Next-generation sequencing (NGS) was performed to screen for serological miRNAs at baseline, month 6, and month 24. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to confirm NGS findings in the entire cohort. Bone turnover markers (BTM) P1NP and CTX, and bone mineral density (BMD) by dual x-ray absorptiometry were assessed and correlated to miRNAs.

Results

BMD at the hip (5.5%, P = 0.0006) and lumbar spine significantly increased (11.4%, P = 0.017), and CTX (64.1%, P < 0.0001) and P1NP (69.3%, P < 0.0001) significantly decreased during treatment. NGS analysis revealed significant changes in miRNAs after 2 years of DMAB treatment but not after 6 months. Seven miRNAs were confirmed by RT-qPCR to be significantly changed during a 2-year course of DMAB treatment compared to baseline. Four of these were mainly transcribed in blood cells, including monocytes. Correlation analysis identified significant correlation between change in miRNA and change in BTMs as well as BMD. Based on effect size and correlation strength, miR-454-3p, miR-26b-5p, and miR-584-5p were defined as top biomarker candidates, with the strongest association to the sustained effect of denosumab on bone in osteoporotic patients.

Conclusion

Two years of DMAB treatment resulted in upregulation of 7 miRNAs, 4 of which are mainly transcribed in monocytes, indicating a potential impact of DMAB on circulating osteoclast precursor cells. These changes were associated to BMD gain and BTM suppression and could therefore be useful for monitoring DMAB treatment response.
Approach to Investigation of Hyperandrogenism in a Postmenopausal Woman
Authors: Hirschberg Angelica Lindén
Published: November 2022

Postmenopausal hyperandrogenism is a condition caused by relative or absolute androgen excess originating from the ovaries and/or the adrenal glands. Hirsutism, in other words, increased terminal hair growth in androgen-dependent areas of the body, is considered the most effective measure of hyperandrogenism in women. Other symptoms can be acne and androgenic alopecia or the development of virilization, including clitoromegaly. Postmenopausal hyperandrogenism may also be associated with metabolic disorders such as abdominal obesity, insulin resistance, and type 2 diabetes. Mild hyperandrogenic symptoms can be due to relative androgen excess associated with menopausal transition or polycystic ovary syndrome, which is likely the most common cause of postmenopausal hyperandrogenism. Virilizing symptoms, on the other hand, can be caused by ovarian hyperthecosis or an androgen-producing ovarian or adrenal tumor that could be malignant. Determination of serum testosterone, preferably by tandem mass spectrometry, is the first step in the endocrine evaluation, providing important information on the degree of androgen excess. Testosterone >5 nmol/L is associated with virilization and requires prompt investigation to rule out an androgen-producing tumor in the first instance. To localize the source of androgen excess, imaging techniques are used, such as transvaginal ultrasound or magnetic resonance imaging (MRI) for the ovaries and computed tomography and MRI for the adrenals. Bilateral oophorectomy or surgical removal of an adrenal tumor is the main curative treatment and will ultimately lead to a histopathological diagnosis. Mild to moderate symptoms of androgen excess are treated with antiandrogen therapy or specific endocrine therapy depending on diagnosis. This review summarizes the most relevant causes of hyperandrogenism in postmenopausal women and suggests principles for clinical investigation and treatment.
Exposure to Childhood Poverty and Racial Differences in Economic Opportunity in Young Adulthood
Authors: Parolin Zachary , Matsudaira Jordan , Waldfogel Jane , Wimer Christopher
Published: November 2022

Young adults in the United States, especially young Black adults, experience high poverty rates relative to other age groups. Prior research has largely attributed racial disparities in young adult poverty to differential attainment of benchmarks related to education, employment, and family formation. This study investigates that mechanism alongside racial differences in childhood poverty exposure. Analyses of Panel Study of Income Dynamics data reveal that racial differences in childhood poverty are more consequential than differential attainment of education, employment, and family formation benchmarks in shaping racial differences in young adult poverty. Whereas benchmark attainment reduces an individual's likelihood of poverty, racial differences in benchmark attainment do not meaningfully explain Black–White poverty gaps for three reasons. First, childhood poverty is negatively associated with benchmark attainment, generating strong selection effects into the behavioral characteristics associated with lower poverty. Second, benchmark attainment does not equalize poverty rates among Black and White men. Third, Black children experience four times the poverty rate of White children, and childhood poverty has lingering negative consequences for young adult poverty. Although equalizing benchmark attainment would reduce Black–White gaps in young adult poverty, equalizing childhood poverty exposure would have twice the reduction effect.
Correlative light and electron microscopy reveals fork-shaped structures at actin entry sites of focal adhesions
Authors: Legerstee Karin , Sueters Jason , Abraham Tsion E. , Slotman Johan A. , Kremers Gert-Jan , Hoogenboom Jacob P. , Houtsmuller Adriaan B.
Published: November 2022

Focal adhesions (FAs) are the main cellular structures to link the intracellular cytoskeleton to the extracellular matrix. FAs mediate cell adhesion, are important for cell migration and are involved in many (patho)-physiological processes. Here we examined FAs and their associated actin fibres using correlative fluorescence and scanning electron microscopy (SEM). We used fluorescence images of cells expressing paxillin-GFP to define the boundaries of FA complexes in SEM images, without using SEM contrast enhancing stains. We observed that SEM contrast was increased around the actin fibre entry site in 98% of FAs, indicating increases in protein density and possibly also phosphorylation levels in this area. In nearly three quarters of the FAs, these nanostructures had a fork shape, with the actin forming the stem and the high-contrast FA areas the fork. In conclusion, the combination of fluorescent and electron microscopy allowed accurate localisation of a highly abundant, novel fork structure at the FA-actin interface.
Kinematic and hydrodynamic analyses of turning manoeuvres in penguins: body banking and wing upstroke generate centripetal force
Authors: Harada Natsuki , Tanaka Hiroto
Published: November 2022

Penguins perform lift-based swimming by flapping their wings. Previous kinematic and hydrodynamic studies have revealed the basics of wing motion and force generation in penguins. Although these studies have focused on steady forward swimming, the mechanism of turning manoeuvres is not well understood. In this study, we examined the horizontal turning of penguins via 3D motion analysis and quasi-steady hydrodynamic analysis. Free swimming of gentoo penguins (Pygoscelis papua) at an aquarium was recorded, and body and wing kinematics were analysed. In addition, quasi-steady calculations of the forces generated by the wings were performed. Among the selected horizontal swimming manoeuvres, turning was distinguished from straight swimming by the body trajectory for each wingbeat. During the turns, the penguins maintained outward banking through a wingbeat cycle and utilized a ventral force during the upstroke as a centripetal force to turn. Within a single wingbeat during the turns, changes in the body heading and bearing also mainly occurred during the upstroke, while the subsequent downstroke accelerated the body forward. We also found contralateral differences in the wing motion, i.e. the inside wing of the turn became more elevated and pronated. Quasi-steady calculations of the wing force confirmed that the asymmetry of the wing motion contributes to the generation of the centripetal force during the upstroke and the forward force during the downstroke. The results of this study demonstrate that the hydrodynamic force of flapping wings, in conjunction with body banking, is actively involved in the mechanism of turning manoeuvres in penguins.
Anti-angiogenic effect of the combination of low-dose sorafenib and EGCG in HCC-induced Wistar rats
Authors: Irawan Andry , Prabowo Erik , Riwanto Ignatius , Atmodjo Wahyuni Lukita
Published: November 2022

Background: 

Sorafenib is a standard drug used for advanced hepatocellular carcinoma but is often resistant and toxic. Its combination with epigallo-3-catechin gallate leads to reduced resistance and toxicity but an equally effective anti-angiogenic effect.Therefore, this study aims to assess the anti-angiogenic effect of standard-dose Sorafenib compared to the combination of low-dose Sorafenib and epigallo-3-catechin gallate.

Methods: 

We conducted an animal study and double-blind, randomized controlled trials. A total of 25 male Wistar rats (7-weeks-old) were randomly divided into four groups, namely Sham (K), Control (O), a combination of low-dose Sorafenib and epigallo-3-catechin gallate group (X1), and standard-dose Sorafenib group (X2). All groups were injected with N-Nitrosodiethylamine 70 mg/kg body weight (BW) intraperitoneally for ten weeks, except the Sham group. After the development of hepatocellular carcinoma, X1 and X2 were treated for two weeks. Subsequently, liver tissues were examined for vascular endothelial growth factor (VEGF) level and microvascular density expression.

Results:

There was a significant difference (p=0.007) in the level of VEGF between group X1 (low dose Sorafenib + EGCG) and X2 (Standard dose Sorafenib). However, the differences in VEGF levels of group X1 and X2 compared to group O(Control) were significantly lower, with values p=0.000136 and p=0.019, respectively. The expression of microvascular density between groups X1 and X2  was not entirely different. Meanwhile, a significant difference (p<0.05) was discovered when both groups were compared with the control group.

Conclusion:

The combination of low-dose Sorafenib with epigallo-3-catechin gallate is superior in reducing the level of VEGF compared to standard-dose Sorafenib and is better than the control. Standard-dose Sorafenib and the combination of low-dose Sorafenib and epigallo-3-catechin gallate have similar effectivity in reducing the expression of microvascular density and could prevent resistance and lower toxicity effects.
Effectiveness of a peanut ball device during labour on maternal and neonatal outcomes: protocol for a randomised controlled trial
Authors: Kamath Pratibha , Pai Muralidhar , Shenoy Revathi , Karkada Sushmitha , D’souza Sonia , Noronha Judith
Published: November 2022

Frequent positional changes and movements during labour is one of the recommendations by the World Health Organization (WHO) to prevent prolonged labour, thereby avoiding cesarean sections. However, labour induction, continuous fetal monitoring in supine position and immobilising the women during labour are standard practices in most private hospitals. To combat these problems and to implement WHO recommendations, the peanut ball is an effective device through which frequent positional changes will be achieved without disrupting the labour procedures. The current study aims to evaluate the effectiveness of the peanut ball device during labour on maternal and neonatal outcomes and assess the stress response induced by labour in terms of maternal and neonatal cortisol in low-risk primigravid women. The study is a prospective, block randomised controlled trial with parallel arms. A total of 768 study participants will be randomised to the peanut-ball group (intervention) and standard care group (control). The intervention group will receive different peanut ball positions during labour at or after 4 cm of cervical dilatation. The primary outcomes of the study are maternal outcome that includes measurement of duration of the active and the second stage of labour, stress level as measured by serum cortisol level at 3–4 cm and at 10 cm of cervical dilatation, mode of delivery, perception of pain, behavioural response during the active stage of labour and neonatal outcomes, which includes the pattern of fetal heart rate, APGAR score, birth injuries, and umbilical serum and salivary cortisol level. The collected data will be compared between the intervention and control groups. 

Trial Registration: This research is registered under the CTRI (Clinical Trials Registry of India) (CTRI/2019/08/020802) (21/8/2019).
The Nigerian youth and their positive attitude towards the national drive against the spread of COVID-19: A cross-sectional online survey
Authors: Jaiyesimi Boluwaji , Bamitale Toba , Diyaolu Babajide , Alabi Kolawole
Published: November 2022

Background: The global impact of coronavirus disease 2019 (COVID-19)has led to the need to prioritise public health campaign by all stakeholders among diverse population groups. This study investigated the dispositions of Nigerian adolescents towards the prevention of the spread of COVID-19. 

Methods: The young adolescents (n=1,529) included in this study, were between the ages of 15 and 26 years from Afe Babalola University. Students were contacted through their various colleges and residential hostels to complete the questionnaire via a shared link. All students included, voluntarily participated in this cross-sectional study by completing the adapted COVID-19 knowledge, attitude and practice (KAP) questionnaire. The collected data were analysed to show the level of knowledge, attitude and preventative practices and also to test for significant association between gender and variables for the study. The study was conducted between March 23-April 25, 2021.

Results: The outcome of the findings showed that students with families with 5-10 members showed significant association with knowledge accuracy on COVID-19 (χ2 = 6.077, p = 0.044). There was a significant association between gender and the need to report the suspected case of COVID-19 infection to the health authorities (χ2 = 14.075, p = 0.001) with more females likely to report a suspected case. More females (59.2%) were significantly (χ2 = 8.904, p = 0.012) involved in the practice of social distancing or home quarantine as a preventive measure.

Conclusions: This study showed evidence of high prevalence of knowledge related to COVID-19 in majority of the study participants. This is a pointer to the efficacy and success of present public health campaigns in Nigeria.
The circadian clock mediates the response to oxidative stress in a cone photoreceptor‒like (661W) cell line via regulation of glutathione peroxidase activity
Authors: Baba Kenkichi , Suen Ting-Chung , Goyal Varunika , Stowie Adam , Davidson Alec , DeBruyne Jason , Tosini Gianluca
Published: November 2022

Background: The mammalian retina contains an autonomous circadian clock that controls many physiological functions within this tissue. Our previous studies have indicated that disruption of this circadian clock by removing Bmal1 from the retina affects the visual function, retinal circuitry, and cone photoreceptor viability during aging. In the present study, we employed a mouse-derived cone photoreceptor‒like cell, 661W, to investigate which molecular mechanisms of the circadian clock may modulate cone photoreceptor viability during aging.

Methods: Bmal1 knockout (BKO) cells were generated from 661W cells using the CRISPR/Cas9 gene editing tool. Deletion of Bmal1 from 661W was verified by western blot and monitoring Per2-luc bioluminescence circadian rhythms. To investigate the effect of Bmal1 removal on an oxidative stress challenge, cells were treated with hydrogen peroxide (H2O2,1 mM) for two hours and then cell viability was assessed. Cells were also cultured and harvested for gene expression analysis and antioxidant assay.

Results: Our data indicated that 661W cells contain a functional circadian clock that mediates the response to an oxidative stress challenge in vitro and that such a response is no longer present in the BKO cell. We also hypothesized that the effect was due to the circadian regulation of the intracellular antioxidant defense mechanism. Our results revealed that in 661W cells, the antioxidant defense mechanism showed time dependent variation , whereas in BKO cells, there was an overall reduction in this antioxidant defense mechanism, and it no longer showed time dependent variation.

Conclusions: Our work supported the notion that the presence of a functional circadian clock and its ability to modulate the response to an oxidative stress is the underlying mechanism that may protect cones during aging.
Students’ Satisfaction Of Online Learning In Oman
Authors: AL-OMAIRI ALHAM RASHID AAMIR , HEW SOON HIN
Published: November 2022

Background: Due to the development facilitated by modern technology, the world has become a small village with instantly changing methods of education. Online education has become an alternative method for course delivery used by colleges and universities globally.  

Methods: The population of this study was N=564 students enrolled in asynchronous online learning at the College of Sharia Sciences in the Sultanate of Oman for the academic year 2020-2021. The survey instruments from “The Student Satisfaction Survey” developed by Strachota (2006) were utilized in this study. The survey included items in the following categories: demographics, learner instructor's interaction, learner-peer interaction, and lastly general satisfaction. The researcher reformulated the questions to suit the target group and some questions were changed to suit the target audience. 

Results: Remarkably, the data show that there is no direct relationship between demographic factors and student satisfaction with asynchronous online learning. On the other hand, there is a strong and noticeable relationship between students' satisfaction with asynchronous online learning and student-instructor interaction. There is also a correlation between students' satisfaction with asynchronous online learning and student-peer interaction.  

Conclusions: The students of the College of Sharia Sciences are on the whole very satisfied with asynchronous online learning; they consider it a very successful experience and recommend its use by students in other educational institutions.
Explaining the unexpected COVID-19 trends and potential impact across Africa.
Authors: Oduro-Mensah Daniel , Oduro-Mensah Ebenezer , Quashie Peter , Awandare Gordon , Okine Laud
Published: November 2022

Official COVID-19 case counts and mortality rates across Africa are lower than had been anticipated. Research reports, however, indicate far higher exposure rates than the official counts in some countries. Particularly in Western and Central Africa, where mortality rates are disproportionately lower than the rest of the continent, this occurrence may be due to immune response adaptations resulting from (1) frequent exposure to certain pro-inflammatory pathogens, and (2) a prevalence of low-grade inflammation coupled with peculiar modifications to the immune response based on one’s immunobiography. We suggest that the two factors lead to a situation where post infection, there is a rapid ramp-up of innate immune responses, enough to induce effective defense and protection against plethora pathogens. Alongside current efforts at procuring and distributing vaccines, we draw attention to the need for work towards appreciating the impact of the apparently widespread, asymptomatic SARS-CoV-2 infections on Africa’s populations vis a vis systemic inflammation status and long-term consequences for public health.