bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor-suppressive circRHOBTB3 is excreted out of cells via exosome to sustain colorectal cancer cell fitness
Authors: Chen Chaoyi , Yu Hongfei , Han Fengyan , Lai Xuan , Ye Kehong , Lei Siqin , Mai Minglang , Lai Maode , Zhang Honghe
Published: February 2022

Background & Aims

To clarify the biological roles, circularization process and secretion pathway of circRHOBTB3 in colorectal cancer (CRC) progression.

Methods

We performed a comprehensive analysis of circRNA levels in serum exosomes from multiple types of cancer patients in public databases and verified the higher level of circRHOBTB3 in CRC sera versus healthy donors by RT-qPCR. Then, the function of circRHOBTB3 in CRC was investigated in vitro and in vivo. RNA-seq and RNA pull-down assays together with mass spectrometry identified the downstream signals and the binding proteins of circRHOBTB3. Finally, Antisense oligonucleotides (ASOs) were designed to target circularization and secretion elements of circRHOBTB3 for CRC therapy.

Results

circRHOBTB3 levels were increased in the sera but was downregulated in tissue samples in CRC, and the downregulation was associated with poor prognosis. Furthermore, circRHOBTB3 acts a tumor-suppressive circRNA by repressing metabolic pathways, intracellular ROS production in CRC. Several key elements were discovered to regulate circRHOBTB3 circularization and exosomal secretion. Moreover, SNF8 was identified that sorts circRHOBTB3 into exosomes. Interestingly, we found that CRC cells could actively secrete more circRHOBTB3 than normal cells. According to the sequence of regulatory elements for circularization and exosomal secretion, we designed and synthesized ASOs, which increased circRHOBTB3 expression and blocked circRHOBTB3 exosomal secretion. More importantly, ASOs could inhibit CRC growth and metastasis in vitro and in vivo.

Conclusions

circRHOBTB3 plays a tumor-suppressive role in CRC and has to be excreted out of cells to sustain cancer cell fitness. ASOs targeting regulatory elements for circularization and exosomal secretion will become a novel antitumor strategy.
Methotrexate-loaded nanoparticles ameliorate experimental model of autoimmune arthritis by regulating the balance of interleukin-17-producing T cells and regulatory T cells
Authors: Park Jin-Sil , Lee Donghyun , Yang SeungCheon , Jeong Ha Yeon , Na Hyun Sik , Cho Keun-Hyung , Choi JeongWon , Koo Heebeom , Cho Mi-La , Park Sung-Hwan
Published: February 2022

Background

Rheumatoid arthritis (RA) is a progressive systemic autoimmune disease that is characterized by infiltration of inflammatory cells into the hyperplastic synovial tissue, resulting in subsequent destruction of adjacent articular cartilage and bone. Methotrexate (MTX), the first conventional disease-modifying antirheumatic drug (DMARD), could alleviate articular damage in RA and is implicated in humoral and cellular immune responses. However, MTX has several side effects, so efficient delivery of low-dose MTX is important.

Methods

To investigate the efficacy of MTX-loaded nanoparticles (MTX-NPs) against experimental model of RA, free MTX or MTX-NPs were administered as subcutaneous route to mice with collagen-induced arthritis (CIA) at 3 weeks after CII immunization. The levels of inflammatory factors in tissues were determined by immunohistochemistry, confocal microscopy, real-time PCR, and flow cytometry.

Results

MTX-NPs ameliorated arthritic severity and joint destruction in collagen-induced arthritis (CIA) mice compared to free MTX-treated CIA mice. The levels of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, and vascular endothelial growth factor, were reduced in MTX-NPs-treated mice. Number of CD4 + IL-17 + cells decreased whereas the number of CD4 + CD25 + Foxp3 + cells increased in spleens from MTX- NPs-treated CIA mice compared to MTX-treated CIA mice. The frequency of CD19 + CD25 + Foxp3 + regulatory B cells increased in ex vivo splenocytes from MTX-loaded NPs-treated CIA mice compared to MTX-treated CIA mice.

Conclusion

The results suggest that MTX-loaded NPs have therapeutic potential for RA.
The influence of timing of coronary angiography on acute kidney injury in out-of-hospital cardiac arrest patients: a retrospective cohort study
Authors: Janssens Gladys N. , Daemen Joost , Lemkes Jorrit S. , Spoormans Eva M. , Janssen Dieuwertje , den Uil Corstiaan A. , Jewbali Lucia S. D. , Heestermans Ton A. C. M. , Umans Victor A. W. M. , Halfwerk Frank R. , Beishuizen Albertus , Nas Joris , Bonnes Judith , van de Ven Peter M. , van Rossum Albert C. , Elbers Paul W. G. , van Royen Niels
Published: February 2022

Background

Acute kidney injury (AKI) is a frequent complication in cardiac arrest survivors and associated with adverse outcome. It remains unclear whether the incidence of AKI increases after the post-cardiac arrest contrast administration for coronary angiography and whether this depends on timing of angiography. Aim of this study was to investigate whether early angiography is associated with increased development of AKI compared to deferred angiography in out-of-hospital cardiac arrest (OHCA) survivors.

Methods

In this retrospective multicenter cohort study, we investigated whether early angiography (within 2 h) after OHCA was non-inferior to deferred angiography regarding the development of AKI. We used an absolute difference of 5% as the non-inferiority margin. Primary non-inferiority analysis was done by calculating the risk difference with its 90% confidence interval (CI) using a generalized linear model for a binary outcome. As a sensitivity analysis, we repeated the primary analysis using propensity score matching. A multivariable model was built to identify predictors of acute kidney injury.

Results

A total of 2375 patients were included from 2009 until 2018, of which 1148 patients were treated with early coronary angiography and 1227 patients with delayed or no angiography. In the early angiography group 18.5% of patients developed AKI after OHCA and 24.1% in the deferred angiography group. Risk difference was − 3.7% with 90% CI ranging from − 6.7 to − 0.7%, indicating non-inferiority of early angiography. The sensitivity analysis using propensity score matching showed accordant results, but no longer non-inferiority of early angiography. The factors time to return of spontaneous circulation (odds ratio [OR] 1.12, 95% CI 1.06–1.19, p < 0.001), the (not) use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (OR 0.20, 95% CI 0.04–0.91, p = 0.04) and baseline creatinine (OR 1.05, 95% CI 1.03–1.07, p < 0.001) were found to be independently associated with the development of AKI.

Conclusions

Although AKI occurred in approximately 20% of OHCA patients, we found that early angiography was not associated with a higher AKI incidence than a deferred angiography strategy. The present results implicate that it is safe to perform early coronary angiography with respect to the risk of developing AKI after OHCA.
Effects of fire history on animal communities: a systematic review
Authors: González Tania Marisol , González-Trujillo Juan David , Muñoz Alberto , Armenteras Dolors
Published: February 2022

Fire is a natural agent with a paramount role in ecosystem functioning and biodiversity maintenance. Still, it can also act as a negative force against many ecosystems. Despite some knowledge of the interactions of fire and vegetation, there is no clear understanding of how different components of fire regimes (i.e., severity, history, or frequency) influence known patterns of animal communities. Therefore, we performed a systematic review on the global responses of arthropods, birds, mammals, reptiles, and amphibians to different fire regimes. Specifically, we focused on assessing how fire severity, history, and frequency modulate the effect of fire on the richness and abundance of faunal communities. We conducted a systematic review of 566 papers retrieved from the Scopus database. We also scrutinized all the documents included in the meta-analysis of Pastro et al. (Pastro et al. Glob Ecol Biogeogr 23:1146–1156, 2014). Our selection criteria excluded studies without data on species richness or abundance. We also excluded studies without adequate controls and those without information about the fire regime of the study zone. After careful examination, we used data from 162 studies to perform a quantitative meta-analysis. From the 162 studies meeting our selection criteria, nearly 60% of the studies are from North America, 25% from Australia, 11% from Europe, and 4% from the tropics. According to the ecological role of fire, 90% of the studies were carried out in fire-dependent ecosystems (i.e., conifer forests, natural savannas, pastures). Finally, 40% of the studies analyzed birds, 22% mammals, and 20% arthropods. The meta-analysis of the available evidence indicates that fire history is an important modulator of animal richness and abundance. Whether negative or positive, animal responses depended on the time since the last fire event. Considering that short-term studies may not capture such a long-term effect on fauna, this translates to more challenges at implementing fire management strategies. Whether or not we can anticipate the impact of the fire will then depend on future efforts to implement long-term research.
Microencapsulated essential oils combined with organic acids improves immune antioxidant capacity and intestinal barrier function as well as modulates the hindgut microbial community in piglets
Authors: Ma Jiayu , Long Shenfei , Wang Jian , Gao Jie , Piao Xiangshu
Published: February 2022

Background

The objective of this experiment was to evaluate the effect of a combination of microencapsulated essential oils and organic acids (MOA) on growth performance, immuno-antioxidant status, intestinal barrier function and microbial structure of the hindgut in piglets. A total of 120 piglets (Duroc × [Landrace × Yorkshire]; weighted 7.66 ± 1.79 kg, weaned at d 28) were randomly selected and allocated to 3 treatments with 4 replicates per group and 10 piglets per replicate according to the initial body weight and gender. The dietary treatments were as follows: 1) basal diet (Ctrl); 2) Ctrl + chlortetracycline (75 mg/kg) (AGP); 3) Ctrl+ MOA (1500 mg/kg). The experiment period was lasted for 21 d.

Results

Compared to the Ctrl group, dietary supplemented MOA alleviated (P < 0.05) the diarrhea rate from d 12 to 21, enhanced (P < 0.05) the concentration of serum interlukin-10 and glutathione peroxidase in piglets on d 11 after weaning and serum superoxide dismutase in 21-day piglets. The MOA group also improved (P < 0.05) the apparent digestibility of dry matter (DM), organic matter (OM) and gross energy (GE), up-regulated (P < 0.05) the mRNA expression level of occludin, claudin-1 and mucin-2 in ileum and increased (P < 0.05) the contents of propionic and butyric acids in the cecum of piglets. The MOA group modulated the cecal and colonic microbial community structure and increased (P < 0.05) the abundance of Faecalibacterium and Muribaculaceae in cecum and Streptococcus and Weissella in colon. Additionally, AGP group decreased (P < 0.05) apparent digestibility of DM, OM and GE as well as down-regulated (P < 0.05) relative gene expression level of claudin-1 in duodenum and jejunum, ZO-1 and mucin-1 in jejunum of piglets.

Conclusion

In summary, dietary supplemented MOA alleviated diarrhea and improved nutrient apparent digestibility in piglets via enhancing immuno-antioxidant properties, increasing digestive enzyme activity, up-regulating the expression of intestinal barrier-related genes, and modifying the microbial community structure of the cecum and colon. Therefore, dietary supplementation with MOA as an alternative to antibiotics was feasible to improve intestinal health of piglets in practical production.
Insects as alternative feed for ruminants: comparison of protein evaluation methods
Authors: Toral Pablo G. , Hervás Gonzalo , González-Rosales Mariana Gabriela , Mendoza Alejandro G. , Robles-Jiménez Lizbeth E. , Frutos Pilar
Published: February 2022

Background

The high dependence of intensive ruminant production on soybean meal and the environmental impact of this crop encourage the search for alternative protein-rich feeds. The use of insects seems promising, but the extent of their ruminal protein degradation is largely unknown. This parameter has major influence not only on N utilization efficiency but also on the environmental burden of ruminant farming. In addition, although assessing ruminal N degradation represents a key first step to examine the potential of new feeds, it is a challenging task due to the lack of a reference method. This study was conducted to investigate the potential of 4 insects (Tenebrio molitor, Zophobas morio, Alphitobius diaperinusandAcheta domesticus) as alternative protein sources for ruminants, using 3 methodologies: 1) a regression technique based on the in vitro relationship between gas production and ammonia-N concentration; 2) a conventional in vitro technique of batch cultures of ruminal microorganisms, based on filtering the incubation residue through sintered glass crucibles; and 3) the in situ nylon bag technique. The in vitro intestinal digestibility of the non-degraded protein in the rumen was also determined. Soybean meal was used as a reference feedstuff.

Results

Comparison of evaluation methods (regression, in vitro and in situ) did not allow to reliably select a single value of ruminal N degradation for the studied substrates, but all techniques seem to establish a similar ranking, with good correlations between methods, particularly between regression and in situ results. Regardless of the methodology, nitrogen from the 4 insects (with contents ranging from 81 to 112 g/kg of dry matter) did not show high ruminal degradation (41–76%), this value being always lower than that of soybean meal. Furthermore, the in vitro intestinal digestibility of non-degraded N was relatively high in all feeds (≥ 64%).

Conclusion

Overall, these results support the potential of the 4 studied insects as alternative feedstuffs for ruminants. Among them,T. molitorshowed the lowest and greatest values of ruminal N degradation and intestinal digestibility, respectively, which would place it as probably the best option to replace dietary soybean meal and increase the sustainability of ruminant feeding.
Relating mathematical abilities to numerical skills and executive functions in informal and formal schooling
Authors: Wongupparaj Peera , Kadosh Roi Cohen
Published: February 2022

Background

The current evidence on an integrative role of the domain-specific early mathematical skills and number-specific executive functions (EFs) from informal to formal schooling and their effect on mathematical abilities is so far unclear. The main objectives of this study were to (i) compare the domain-specific early mathematics, the number-specific EFs, and the mathematical abilities between preschool and primary school children, and (ii) examine the relationship among the domain-specific early mathematics, the number-specific EFs, and the mathematical abilities among preschool and primary school children.

Methods

The current study recruited 6- and 7-year-old children (Ntotal = 505, n6yrs = 238, and n7yrs = 267). The domain-specific early mathematics as measured by symbolic and nonsymbolic tasks, number-specific EFs tasks, and mathematics tasks between these preschool and primary school children were compared. The relationship among domain-specific early mathematics, number-specific EFs, and mathematical abilities among preschool and primary school children was examined. MANOVA and structural equation modeling (SEM) were used to test research hypotheses.

Results

The current results showed using MANOVA that primary school children were superior to preschool children over more complex tests of the domain-specific early mathematics; number-specific EFs; mathematical abilities, particularly for more sophisticated numerical knowledge; and number-specific EF components. The SEM revealed that both the domain-specific early numerical and the number-specific EFs significantly related to the mathematical abilities across age groups. Nevertheless, the number comparison test and mental number line of the domain-specific early mathematics significantly correlated with the mathematical abilities of formal school children. These results show the benefits of both the domain-specific early mathematics and the number-specific EFs in mathematical development, especially at the key stages of formal schooling. Understanding the relationship between EFs and early mathematics in improving mathematical achievements could allow a more powerful approach in improving mathematical education at this developmental stage.
Rapid and simple LC–MS/MS determination of urinary ethyl glucuronide, naltrexone, 6β-naltrexol, chlordiazepoxide, and norchlordiazepoxide for monitoring alcohol abuse
Authors: Sim Yeong Eun , Kim Ji Woo , Ko Beom Jun , Kim Jin Young
Published: February 2022

In this study, a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed to detect ethyl glucuronide (EtG), which is a biomarker for monitoring alcohol consumption, and naltrexone (NTX), 6β-naltrexol (6βNTX), chlordiazepoxide (CDP), and norchlordiazepoxide (norCDP), which are analyzed to confirm the presence of medications for alcohol dependence treatment. The protein precipitation method was conducted to rapidly prepare samples. LC–MS/MS analysis was performed in the multiple-reaction monitoring mode. The analytes were separated using a Scherzo SM-C18 (2.0 × 100 mm, 3 µm) column. The calibration ranges were 5–1000 ng/mL for EtG, 6βNTX, CDP, and norCDP, and 1–100 ng/mL for NTX, with the correlation coefficients (r) being ≥ 0.994, and the weighting factor being 1/x2. The lower limit of quantification was 1–5 ng/mL. The method was also validated for precision, accuracy, selectivity, dilution integrity, recovery, matrix effect, and stability. The developed method was successfully applied for the determination of EtG, NTX, 6βNTX, CDP, and norCDP in urine samples obtained from 49 probationers who received alcohol dependence treatment orders. The method developed herein can be used to monitor the drug-based treatment of alcohol abuse and alcohol consumption during the treatment of individuals under probation.
Pharmacokinetics, bioavailability and tissue distribution of chitobiose and chitotriose in rats
Authors: Chen Mai , Jin Jiayang , Ji Xiaoguo , Chang Kunlin , Li Juan , Zhao Liming
Published: February 2022

Chitooligosaccharides (COSs) have various physiological activities and broad application prospects; however, their pharmacokinetics and tissue distribution remain unclear. In this study, a sensitive and selective ultra-performance liquid chromatography–mass spectrometry (UPLC–MS) method for determining chitobiose (COS 2) and chitotriose (COS 3) in rat serum and tissues was developed. This method was successfully validated based on FDA guidelines in terms of selectivity, calibration curves (lower limit of quantification was 0.002 µg/mL for COS 2 and 0.02 µg/mL for COS 3), precision (intra-day relative standard deviation of 0.04%–3.55% and inter-day relative standard deviation of 1.94%–11.63%), accuracy (intra-day relative error of − 1.81%–11.06% and inter-day relative error of − 9.41%–8.63%), matrix effects, recovery (97.10%–101.29%), stability, dilution integrity, and carry-over effects. Then, the method was successfully applied to the pharmacokinetics and tissue distribution study of COS 2 and COS 3 after intragastric and intravenous administration. After intragastric administration, COS 2 and COS 3 were rapidly absorbed, reached peak concentrations in the serum after approximately 0.45 h, and showed rapid elimination with clearances greater than 18.82 L/h/kg and half-lives lower than 6 h. The absolute oral bioavailability of COS 2 and COS 3 was 0.32%–0.52%. COS 2 and COS 3 were widely distributed in Wistar rat tissues and could penetrated the blood–brain barrier without tissue accumulation.

Graphic Abstract
Enzymatic synthesis of a novel solid–liquid phase change energy storage material based on levulinic acid and 1,4-butanediol
Authors: Zhai Siyu , Zhang Lihe , Zhao Xi , Wang Qian , Yan Yin , Li Cui , Zhang Xu
Published: February 2022

The current energy crisis has prompted the development and utilization of renewable energy and energy storage material. In this study, levulinic acid (LA) and 1,4-butanediol (BDO) were used to synthesize a novel levulinic acid 1,4-butanediol ester (LBE) by both enzymatic and chemical methods. The enzymatic method exhibited excellent performance during the synthesis process, and resulted in 87.33% of LBE yield, while the chemical method caused more by-products and higher energy consumption. What’s more, the thermal properties of the obtained LBE as a phase change material (PCM) were evaluated. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) showed that the melting temperature, latent heat of melting, and pyrolysis temperature were 50.51 °C, 156.1 J/g, and 150–160 °C, respectively. Compared with the traditional paraffin, the prepared PCM has a superior phase transition temperature, a higher latent heat of melting, and better thermal stability. The thermal conductivity could be increased to 0.34 W/m/k after adding expanded graphite (EG). In summary, LBE has great potential in the application of energy storage as a low-temperature phase change energy storage material.

Graphical Abstract
Biomechanical finite element analysis of short-implant-supported, 3-unit, fixed CAD/CAM prostheses in the posterior mandible
Authors: Zupancic Cepic Lana , Frank Martin , Reisinger Andreas , Pahr Dieter , Zechner Werner , Schedle Andreas
Published: February 2022

Objective

To assess the biomechanical effects of different prosthetic/implant configurations and load directions on 3-unit fixed prostheses supported by short dental implants in the posterior mandible using validated 3-D finite element (FE) models.

Methods

Models represented an atrophic mandible, missing the 2nd premolar, 1st and 2nd molars, and rehabilitated with either two short implants (implant length-IL = 8 mm and 4 mm) supporting a 3-unit dental bridge or three short implants (IL = 8 mm, 6 mm and 4 mm) supporting zirconia prosthesis in splinted or single crowns design. Load simulations were performed in ABAQUS (Dassault Systèmes, France) under axial and oblique (30°) force of 100 N to assess the global stiffness and forces within the implant prosthesis. Local stresses within implant/prosthesis system and strain energy density (SED) within surrounding bone were determined and compared between configurations.

Results

The global stiffness was around 1.5 times higher in splinted configurations vs. single crowns, whereby off-axis loading lead to a decrease of 39%. Splinted prostheses exhibited a better stress distribution than single crowns. Local stresses were larger and distributed over a larger area under oblique loads compared to axial load direction. The forces on each implant in the 2-implant-splinted configurations increased by 25% compared to splinted crowns on 3 implants. Loading of un-splinted configurations resulted in increased local SED magnitude.

Conclusion

Splinting of adjacent short implants in posterior mandible by the prosthetic restoration has a profound effect on the magnitude and distribution of the local stress peaks in peri-implant regions. Replacing each missing tooth with an implant is recommended, whenever bone supply and costs permit.
Feasibility trial of an integrated treatment “Activate for Life” for physical and mental well-being in older adults
Authors: Hernandez-Tejada Melba A. , Nagel Alexis , Madisetti Mohan , Balasubramanian Sundar , Kelechi Teresa
Published: February 2022

Background

Pain and fatigue are common chronic conditions faced by older adults. Integrated interventions to address pain and fatigue may therefore be particularly useful for older adults, especially those interventions that target mobility and psychosocial well-being. The present study describes feasibility and participant satisfaction for an integrated eHealth treatment to address pain and fatigue in a sample of older adults living in a low-income independent residence facility and their own homes in the community.

Methods

Three treatment combinations were compared in a randomized repeated measures design to determine if adding components of breathing retraining and behavioral activation to the existing Otago program (for strength and balance) affected feasibility and patient satisfaction. Specifically, 30 older adults were randomly allocated to: Arm1: the Otago alone (n = 10); Arm 2: Otago + Gentle Yoga and Yogic Breathing (n = 10); or Arm 3: Otago + Gentle Yoga and Yogic Breathing + Behavioral Activation (combination was named ‘Activate for Life’ n = 10). Feasibility measures included recruitment rate, session completion characteristics, and satisfaction with the program.

Conclusion

Data from this study provide support for the feasibility of an integrated program to address physical and mental well-being of older adults. Future fully powered studies should now focus on assessment of clinical outcomes and refinement of individual components.

Trial registration

Registered in clinicaltrials.gov with the identifier: NCT03853148.
Healthcare experiences of uninsured and under-insured American Indian women in the United States
Authors: Liddell Jessica L. , Lilly Jenn M.
Published: February 2022

Background

Extensive health disparities exist for American Indian groups throughout the United States. Although insurance status is linked to important healthcare outcomes, this topic has infrequently been explored for American Indian tribes. For state-recognized tribes, who do not receive healthcare services through the Indian Health Service, this topic has yet to be explored. The purpose of this study is to explore how having limited access to health insurance (being uninsured or under-insured) impact American Indian women's healthcare experiences?.

Methods

In partnership with a community advisory board, this study used a qualitative description approach to conduct thirty-one semi-structured life-course interviews with American Indian women who are members of a state-recognized tribe in the Gulf Coast (United States) to explore their Western healthcare experiences. Interview were conducted at community centers, participant homes, and other locations identified by participants. Interviews were transcribed verbatim and findings were analyzed in NVivo using conventional content analysis. Findings were presented at tribal council meetings and to participants for member checking.

Results

Themes identified by participants included: (a) lack of insurance as a barrier to healthcare; (b) pre-paying for childbirth when uninsured; and (c) access to public health insurance coverage. Twenty-four women mentioned the role or importance of insurance in discussing their healthcare experiences, which was referenced a total of 59 times.

Conclusion

These findings begin to fill an important gap in the literature about the health insurance experiences of American Indian tribal members. Not having insurance was an important concern for participants, particularly for elderly and pregnant tribal members. Not having insurance also kept tribal members from seeking healthcare services, and from getting needed prescriptions. In addition to promoting knowledge about, and expanding insurance options and enrollment, increased sovereignty and resources for state-recognized tribes is needed to address the health disparities experienced by American Indian groups.
Assessment and validation of the Community Maternal Danger Score algorithm
Authors: Bola Rajan , Ujoh Fanan , Ukah Ugochinyere Vivian , Lett Ronald
Published: February 2022

Background

High rates of maternal mortality in low-and-middle-income countries (LMICs) are associated with the lack of skilled birth attendants (SBAs) at delivery. Risk analysis tools may be useful to identify pregnant women who are at risk of mortality in LMICs. We sought to develop and validate a low-cost maternal risk tool, the Community Maternal Danger Score (CMDS), which is designed to identify pregnant women who need an SBA at delivery.

Methods

To design the CMDS algorithm, an initial scoping review was conducted to identify predictors of the need for an SBA. Medical records of women who delivered at the Federal Medical Centre in Makurdi, Nigeria (2019–2020) were examined for predictors identified from the literature review. Outcomes associated with the need for an SBA were recorded: caesarean section, postpartum hemorrhage, eclampsia, and sepsis. A maternal mortality ratio (MMR) was determined. Multivariate logistic regression analysis and area under the curve (AUC) were used to assess the predictive ability of the CMDS algorithm.

Results

Seven factors from the literature predicted the need for an SBA: age (under 20 years of age or 35 and older), parity (nulliparity or grand-multiparity), BMI (underweight or overweight), fundal height (less than 35 cm or 40 cm and over), adverse obstetrical history, signs of pre-eclampsia, and co-existing medical conditions. These factors were recorded in 589 women of whom 67% required an SBA (n = 396) and 1% died (n = 7). The MMR was 1189 per 100,000 (95% CI 478–2449). Signs of pre-eclampsia, obstetrical history, and co-existing conditions were associated with the need for an SBA. Age was found to interact with parity, suggesting that the CMDS requires adjustment to indicate higher risk among younger multigravida and older primigravida women. The CMDS algorithm had an AUC of 0.73 (95% CI 0.69–0.77) for predicting whether women required an SBA, and an AUC of 0.85 (95% CI 0.67–1.00) for in-hospital mortality.

Conclusions

The CMDS is a low-cost evidence-based tool that uses 7 risk factors assessed on 589 women from Makurdi. Non-specialist health workers can use the CMDS to standardize assessment and encourage pregnant women to seek an SBA in preparation for delivery, thus improving care in countries with high rates of maternal mortality.
Vascular dysfunction and dyslipidemia in multiple sclerosis: are they correlated with disease duration and disability status?
Authors: Boshra Hesham , Awad Marina , Hussein Mona , Elyamani Ehab
Published: February 2022

Background

There is strong evidence that vascular dysfunction is considered one of the possible causes of morbidity and mortality in patients suffering from multiple sclerosis (MS). This work aimed at assessing the arterial function and serum lipids in MS patients and correlating them with clinical and radiological findings.

Results

This case–control study included 50 patients with MS and 50 age- and sex-matched controls. The arterial function was significantly reduced in MS patients, confirmed by significantly higher pulse wave velocity (PWV) and augmentation index (AIX), while the carotid IMT did not show significant difference between the two groups with no plaques in any of our patients. A significant positive correlation was found between PWV and both disease duration and disability. MS patients had significantly higher serum levels of T-cholesterol and triglycerides, and significantly lower serum levels of HDL-cholesterol, compared to controls. No significant correlation was found between serum lipids and either disease duration or disability.

Conclusions

There was a significant impairment in arterial function (assessed by the brachial cuff-based method via Mobil-O-Graph device) in MS patients compared to controls. Such impairment was significantly correlated with both disease duration and disability. MS patients had also significantly higher levels of T-cholesterol and triglycerides, compared to controls with no significant correlation between serum lipids and either disease duration or disability.
Cross-cultural comparison of depressive symptoms on the Beck Depression Inventory-II, across six population samples
Authors: Seppänen Marjo , Lankila Tiina , Auvinen Juha , Miettunen Jouko , Korpelainen Raija , Timonen Markku
Published: February 2022

Background

The Beck Depression Inventory (BDI) and BDI-II (revised version) are some of the most widely used and comparable self-report scales for assessing the presence and severity of depressive symptoms in many countries. However, although the relative mean score of each symptom in different countries may vary, the cultural differences of BDI-II symptoms for each item have not been previously studied.

Aims

To examine the overall picture of the magnitude of the symptoms in the Finnish population, and compare the relative mean score of each symptom between all published population-based samples from different countries fulfilling the search criteria.

Method

We conducted a search for population-based studies reporting BDI-II item, using Scopus, PsycINFO and PubMed, and five population-based samples were identified. Relative average scores for each item of the scale were calculated for the Finnish population and five populations from other countries. Meta-regression methods were used to test the differences in the relative score of each symptom between each country separately, and results were then visually compared with spider charts.

Results

We found significant differences in several BDI-II item scores between countries: lower indecisiveness, higher changes in sleep pattern and higher irritability in Finland; higher loss of pleasure in Norway; higher loss of interest in the Dominic Republic; higher self-criticalness and feelings of punishment in Mexico; and higher sadness in Japan.

Conclusions

Based on the study fundings and including all currently published population-based samples with BDI-II scores, cultural differences in depressive symptoms should be considered when interpreting BDI-II item scores.
Consistent brain structural abnormalities and multisite individualised classification of schizophrenia using deep neural networks
Authors: Cui Yue , Li Chao , Liu Bing , Sui Jing , Song Ming , Chen Jun , Chen Yunchun , Guo Hua , Li Peng , Lu Lin , Lv Luxian , Ning Yuping , Wan Ping , Wang Huaning , Wang Huiling , Wu Huawang , Yan Hao , Yan Jun , Yang Yongfeng , Zhang Hongxing , Zhang Dai , Jiang Tianzi
Published: February 2022

Background

Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.

Aims

To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.

Method

We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.

Results

We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.

Conclusions

These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
Preoperative Thoracic Muscle Mass Predicts Bone Density Change After Parathyroidectomy in Primary Hyperparathyroidism
Authors: Burm Seung Won , Hong Namki , Lee Seunghyun , Kim Gi Jeong , Hwang Sang Hyun , Jeong Jongju , Rhee Yumie
Published: February 2022

Context

Predicting bone mineral density (BMD) gain after parathyroidectomy may influence individualized therapeutic approaches for treating patients with primary hyperparathyroidism (PHPT).

Objective

This study aimed to assess whether skeletal muscle mass data could predict BMD change after parathyroidectomy in patients with PHPT.

Methods

This retrospective study collected data from 2012 to 2021 at Severance Hospital, Seoul, Korea. A total of 130 patients (mean age, 64.7 years; 81.5% women) with PHPT who underwent parathyroidectomy were analyzed. Thoracic muscle volume (T6-T7 level) was estimated using noncontrast parathyroid single photon emission computed tomography/computed tomography (SPECT/CT) scans and an automated deep-learning–based software. The primary outcome assessed was the change in femoral neck BMD (FNBMD, %) 1 year after parathyroidectomy.

Results

The median degree of FNBMD change after parathyroidectomy was + 2.7% (interquartile range: –0.9 to + 7.6%). Elevated preoperative PTH level was associated with lower thoracic muscle mass (adjusted β: –8.51 cm3 per one log-unit PTH increment, P = .045) after adjusting for age, sex, body mass index (BMI), and baseline FNBMD. One SD decrement in thoracic muscle mass was associated with lesser FNBMD (adjusted β: –2.35%, P = .034) gain and lumbar spine BMD gain (adjusted β: –2.51%, P = .044) post surgery after adjusting for covariates.

Conclusion

Lower thoracic skeletal muscle mass was associated with elevated preoperative PTH levels in patients with PHPT. Lower skeletal muscle mass was associated with lesser BMD gain after parathyroidectomy, independent of age, sex, BMI, preoperative BMD, and PTH level.
Insights From Long-term Follow-up of a Girl With Adrenal Insufficiency and Sphingosine-1-Phosphate Lyase Deficiency
Authors: Maharaj Avinaash , Güran Tülay , Buonocore Federica , Achermann John C , Metherell Louise , Prasad Rathi , Çetinkaya Semra
Published: February 2022

Introduction

Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is a multisystemic disorder which, in the main, incorporates steroid-resistant nephrotic syndrome and primary adrenal insufficiency (PAI).

Case Presentation

We present a young girl with a novel homozygous variant in SGPL1, p.D350G, with PAI in the absence of nephrotic syndrome. In the course of 15 years of follow-up she has further developed primary hypothyroidism and while she has progressed through puberty appropriately, ovarian calcifications were noted on imaging. The p.D350G variant results in reduced protein expression of SGPL1. We demonstrate that CRISPR engineered knockout of SGPL1 in human adrenocortical (H295R) cells abrogates cortisol production. Furthermore, while wild-type SGPL1 is able to rescue cortisol production in this in vitro model of adrenal disease, this is not observed with the p.D350G mutant.

Conclusion

SGPL1 deficiency should be considered in the differential diagnosis of PAI with close attention paid to evolving disease on follow-up.
Safety and Efficacy of Burosumab in Pediatric Patients With X-Linked Hypophosphatemia: A Phase 3/4 Open-Label Trial
Authors: Namba Noriyuki , Kubota Takuo , Muroya Koji , Tanaka Hiroyuki , Kanematsu Masanori , Kojima Masahiro , Orihara Shunichiro , Kanda Hironori , Seino Yoshiki , Ozono Keiichi
Published: February 2022

Objective

Burosumab, an anti-fibroblast growth factor 23 antibody, was recently approved for the treatment of X-linked hypophosphatemia (XLH).

We evaluated the safety and efficacy of burosumab in pediatric XLH patients.

Methods

This open-label, phase 3/4 trial of ≤ 124 weeks’ duration was conducted at 4 Japanese medical centers. Fifteen children aged 1 to 12 years with XLH were included. All had previously been treated with phosphorus or vitamin D. Subcutaneous burosumab was administered every 2 weeks, starting with 0.8 mg/kg, and adjusted based on serum phosphorus levels and any safety concerns (maximum 2 mg/kg). Safety assessments included the frequency of treatment-emergent adverse events (TEAEs). Efficacy of burosumab on biochemical markers, clinical markers of rickets, motor function, and growth was also evaluated.

Results

The average treatment duration was 121.7 weeks. Frequently reported TEAEs were nasopharyngitis (46.7%), dental caries (40.0%), and influenza (33.3%). At baseline, patients had low serum phosphorus concentrations (2.6 ± 0.3 mg/dL) and low-to-normal 1,25-dihydroxyvitamin D concentrations (24.7 ± 12.7 pg/mL), which increased with burosumab treatment and were maintained during the study period. Alkaline phosphatase decreased continuously. At baseline, the mean ± SD total Thacher Rickets Severity Score (RSS) was 1.3 ± 1.2, and 4 patients (26.7%) had an RSS ≥ 2.0. Mean Radiographic Global Impression of Change and RSS tended to improve, particularly in patients with higher baseline RSS. There was a trend toward increased 6-minute walk test distance. No apparent changes in growth rate were observed.

Conclusion

Burosumab has a good safety profile and is effective in pediatric patients with XLH.
The Utility of Intraoperative Magnetic Resonance Imaging in the Resection of Cerebellar Hemispheric Pilocytic Astrocytomas: A Cohort Study
Authors: Hamilton Kimberly M. , Malcolm James G. , Desai Sona , Reisner Andrew , Chern Joshua J.
Published: February 2022

BACKGROUND:

The mainstay of treatment for cerebellar pilocytic astrocytomas in the pediatric population is surgery. The use of intraoperative magnetic resonance imaging (iMRI) as a surgical adjunct may lower the likelihood of reoperation. Studies have examined iMRI in heterogenous tumor populations, but few have looked at single pathologies.

OBJECTIVE:

To compare iMRI vs non-iMRI for hemispheric cerebellar pilocystic astrocytomas, specifically looking at revision surgeries and residual disease in follow-up.

METHODS:

Retrospective review of medical records for 60 sequential patients with cerebellar hemispheric pilocytic astrocytoma at a single institution was conducted. Thirty-two patients with cerebellar pilocytic astrocytoma underwent surgery without iMRI, whereas 28 patients underwent surgical resection with iMRI. All patients had at least 3-year follow-up.

RESULTS:

There were no significant differences between the patient populations in age, tumor size, or need for cerebrospinal fluid diversion between groups. Operative time was shorter without iMRI (without iMRI 4.4 ± 1.3 hours, iMRI 6.1 ± 1.5, P = .0001). There was no significant difference in the patients who had repeat surgery within 30 days (9% without iMRI, 0% iMRI, P = .25), residual disease at 3 months (19% without iMRI, 14% iMRI, P = .78), or underwent a second resection beyond 30 days (9% without iMRI, 4% iMRI, P = .61). There were more total reoperations in the group without iMRI, although this did not reach significance (19% vs 4%, P = .11).

CONCLUSION:

For hemispheric cerebellar pilocytic astrocytomas, iMRI tended to leave less residual and fewer reoperations; however, neither of these outcomes achieved statistical significance leaving utilization to be determined by the surgeon.
Effect of heterogeneous substrate adhesivity of follower cells on speed and tension profile of leader cells in primary keratocyte collective cell migration
Authors: Chakraborty Madhura , Mukherjee Baishali , Nalinakshan Nanditha , Biswas Arikta , Nayak Rajesh Kumble , Sinha Bidisha
Published: February 2022

In single keratocyte motility, membrane tension is reported to be high at cell-fronts and believed to establish front coherence. To understand role of membrane mechanics in collective cell migration, we study membrane height fluctuations in cell sheets from fish scales using interference reflection microscopy (IRM). We report the monolayer to have cells lacking substrate adhesion and show that such ‘non-sticky’ cells can form bridges between leader cells and far-away follower cells. Do such interactions alter motility and membrane mechanics in such leaders? We find non-significant, but reduced speed for leaders with ‘non-sticky’ followers in comparison to other leaders. Cells show high phenotypic variability in their membrane fluctuation tension profiles. On average, this tension is found to be lower at cell fronts than the mid-section. However, leaders with non-sticky followers are more prone to display higher tension at their front and have a negative correlation between cell speed and front-mid tension difference. Thus, we conclude that intracellular tension gradients are heterogeneous in cell sheets and substrate adhesivity of followers can control the coupling of the gradient to cell speed.
Expression levels and activities of energy-yielding ATPases in the oligohaline neritid snail Theodoxus fluviatilis under changing environmental salinities
Authors: Knobloch Jan , Müller Christian , Hildebrandt Jan-Peter
Published: February 2022

The aquatic gastropod Theodoxus fluviatilis occurs in Europe and adjacent areas of Asia. The snail species has formed two genetically closely related subgroups, the freshwater ecotype (FW) and the brackish water ecotype (BW). Other than individuals of the FW ecotype, those of the BW ecotype survive in salinities of up to 28‰. Coastal aquatic ecosystems may be affected by climate change due to salinization. Thus, we investigated how the two Theodoxus ecotypes adjust to changes in environmental salinity, focusing on the question whether Na+/K+-ATPase or V-ATPase are regulated on the transcriptional, the translational or at the activity level under changing external salinities. Animals were gradually adjusted to extreme salinities in containers under long-day conditions and constant temperature. Whole body RNA- or protein extracts were prepared. Semi-quantitative PCR- and western blot-analyses did not reveal major changes in transcript or protein abundances for the two transporters under low or high salinity conditions. No significant changes in ATPase activities in whole body extracts of animals adjusted to high or low salinity conditions were detected. We conclude that constitutive expression of ATPases is sufficient to support osmotic and ion regulation in this species under changing salinities given the high level of tolerance with respect to changes in body fluid volume.