Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolution of osmosensing OSCA1 Ca2+ channel family coincident with plant transition from water to land

Water is crucial to plant growth, development, and environmental adaptation. Water stress triggers cytosolic Ca2+ ([Ca2+]i) increases, and the osmosensor OSCA1 (REDUCED‐HYPEROSMOLALITY‐INDUCED‐[Ca2+]i‐INCREASE 1), a member of the OSCA family, perceives the initial water stress and governs its downstream responses. OSCA homologs exist in eukaryotes and largely radiate in higher plants. However, it is enigmatic whether the OSCA family is crucial for plant evolution from aqueous to terrestrial environments and for the subsequent adaptation on land. Here, we carried out the first phylogenetic and molecular evolutionary analyses of the OSCA family. The family originated and diversified during the early evolution of protists, and three more lineages were established (a) in plants, (b) in fungi, and (c) in a complex clade of several major eukaryotic lineages. The chlorophyte algal cluster is directly basal to streptophyte‐specific Clades 1–3, consistent with plant transition from water to land. The Clades 1–3 present different gene expansion pattern and together with previous functional analysis of OSCAs reveal that they probably have evolved diverse functions in respond to various mechanical stresses during the independent evolution of land plant clades. Moreover, variable selection pressures on different land plant lineages were explored. OSCAs in early land plants (mosses and lycophytes) were under decelerated evolution, whereas OSCAs in seed plants showed accelerated evolution. Together, we hypothesize OSCAs have evolved to sense water stress in the ancestor of euphyllophytes, which occupies typical leaves, typical roots, and phloem tissues, all of which require osmosensors to maintain water balance and food conduction through plant bodies.
Efficacy and safety profile of antioxidants in the treatment of atopic dermatitis: A systematic review and meta‐analysis of randomized controlled trials

The use of antioxidants in atopic dermatitis (AD) is controversial. We conducted a systematic review and meta‐analysis to evaluate the efficacy and safety of antioxidants therapy in AD. Randomized clinical trials were identified from Medline, Embase, and Cochrane library. Changes from baseline in severity and itch score were extracted from individual studies and pooled using random‐effects. Eighteen trials including 763 AD patients were eligible. Overall, antioxidants were associated with statistically significant reductions in diseases severity (p < 0.0001), but not with itch score (p = 0.59). No serious adverse events were recorded. Subgroup analyses revealed that antioxidants were associated with a significant reduction in severity score regardless of disease severity at baseline and treatment duration (p < 0.05). However, antioxidants had additional benefit only in children (p = 0.02) but not in adults (p = 0.30). Oral supplementation with vitamin D, combined vitamins D and E, combined vitamins A, D and E and topical vitamin B12 was associated with significantly lower severity score (p < 0.05). There was significant heterogeneity between studies (I2 = 50%; p = 0.003). The effect estimates did not change statistically after excluding sources of study heterogeneity. This meta‐analysis suggests that antioxidants may be a safe and effective treatment for AD patients, especially when supplemented with oral vitamin D and topical vitamin B12, as well as in pediatric patients.
Cystic fibrosis year in review 2021

People with cystic fibrosis (CF) have an amazing outlook with the treatment availability of highly effective modulators. Unfortunately, not all people with CF are eligible for modulators leading to continued pulmonary exacerbations and advanced lung disease. Additionally, optimizing diagnosis and evaluation for CF in the newborn period continues to be an area of focus for research. This review article will work to cover articles published in 2021 with high clinical relevance related to the above topics; however, due to the extensive body of research published, this review will not be comprehensive.
Dielectric Modulated Nanotube Tunnel Field-Effect Transistor as a Label Free Biosensor: Proposal and Investigation

Dielectric modulated (DM) field-effect transistors (FET) have gained significant popularity for label-free detection of biomolecules. However, the inherent short channel effects limit their sensitivity, scalability and energy-efficiency. Therefore, to realize the true potential of the DMFET based biosensors, in this work, we propose a highly scalable, extremely sensitive and energy-efficient DM nanotube tunnel FET (NT-TFET) biosensor for label-free detection of biomolecules by modifying the structure of the conventional NT-TFET. The modified architecture facilitates the realization of a nanocavity at the source-channel tunneling junction and also provides stability to the immobilized biomolecules. We have performed an extensive analysis of the performance of the proposed DM NT-TFET biosensor in the presence of different representative target biomolecules characterized by different dielectric constants, and/or ionized charge densities using calibrated TCAD simulations. Our results indicate that the proposed DM NT-TFET exhibits an extremely high threshold voltage sensitivity (<inline-formula> <tex-math notation="LaTeX">${S}_{{V}_{{{th}}}}$ </tex-math></inline-formula>) of 0.44, a high selectivity exceeding four orders of magnitude, ON-state current sensitivity (<inline-formula> <tex-math notation="LaTeX">$\textrm {S}_{\textrm {I}_{{{ON}}}}$ </tex-math></inline-formula>) of more than five orders of magnitude and could be a promising alternative to the conventional FET based dielectric modulated biosensors. Moreover, the sensitivity of the proposed DM NT-TFET could be further improved by utilizing alternate source materials with lower bandgap or by probing the transient response of the drain current and exploiting the difference in the settling time for different biomolecules with different dielectric constant (<inline-formula> <tex-math notation="LaTeX">$\kappa$ </tex-math></inline-formula>).
Postnatal development of the enteric neurons expressing neuronal nitric oxide synthase

Neurons, expressing neuronal nitric oxide synthase (nNOS) in the enteric ganglia are inhibitory motor neurons or interneurons. The aim of the study was to identify the percentage, cross‐sectional area of nNOS‐immunoreactive (IR) neurons and their colocalization with choline acetyltransferase (ChAT), vasoactive intestinal polypeptide (VIP), and neuropeptide Y in the intramural ganglia of the myenteric (MP) and submucous plexus (SP) of the small intestine (SI) and large intestine (LI) of rats of different age groups using immunohistochemical methods. In the intramural ganglia of the MP, the largest percentage of nNOS‐IR neurons was detected in newborn rats in the LI (81 ± 0.9%) and SI (48 ± 4.1%). Subsequently, it decreased in ontogenesis up to 60 days of life (26 ± 0.9% LI, 29 ± 3.2% SI), and did not change until senescence. In the SP, abundant nNOS‐IR neurons were also detected in newborns (82 ± 7.0% SI, 85 ± 3.2% LI), while their percentage decreased significantly in the next 20 days. Furthermore, a very small number of nNOS‐IR neurons was detected in 30‐day‐ and 2‐month‐old animals, but they again appeared in large numbers in aged rats. In the MP, the highest percentage of nNOS+/ChAT+ neurons was in 1‐day‐old, 10‐day‐old, and 2‐year‐old rats. In the SP, the largest number of nNOS‐IR neurons colocalized ChAT regardless of age. In the MP of all rats, many nNOS‐IR neurons colocalized VIP, and the maximal percentage of nNOS+/VIP+ neurons was found in 2‐year‐old rats, minimal—in newborns. In conclusion, nNOS expression in neurons of the gut is decreased in early postnatal ontogenesis and subsequently increased in aged rats.
Incredible affinity of Kattosh with PPAR‐γ receptors attenuates STZ‐induced pancreas and kidney lesions evidenced in chemicobiological interactions

Since ancient times, plants have been used as green bioresources to ensure a healthier life by recovering from different diseases. Kattosh (Lasia spinosa L. Thwaites) is a local plant with various traditional uses, especially for arthritis, constipation and coughs. This research investigated the effect of Kattosh stem extract (LSES) on streptozotocin‐induced damage to the pancreas, kidney, and liver using in vitro, in vivo and in silico methods. In vitro phytochemical, antioxidative and anti‐inflammatory effects of LSES were accomplished by established methods followed by antidiabetic actions in in vivo randomized controlled intervention in STZ‐induced animal models for four weeks. In an in silico study, LSES phytocompounds interacted with antidiabetic receptors of peroxisome proliferator‐activated receptor‐gamma (PPAR, PDB ID: 3G9E), AMP‐activated protein kinase (AMPK, PDB ID: 4CFH) and α‐amylase enzyme (PDB ID: 1PPI) to verify the in vivo results. In addition, LSES showed promising in vitro antioxidative and anti‐inflammatory effects. In contrast, it showed a decrease in weekly blood glucose level, normalized lipid profile, ameliorated liver and cardiac markers, managed serum AST and ALT levels, and increased glucose tolerance ability in the animal model study. Restoration of pancreatic and kidney damage was reflected by improving histopathological images. In ligand–receptor interaction, ethyl α‐d‐glucopyranoside of Kattosh showed the highest affinity for the α‐amylase enzyme, PPAR, and AMPK receptors. Results demonstrate that the affinity of Kattosh phytocompounds potentially attenuates pancreatic and kidney lesions and could be approached as an alternative antidiabetic source with further clarification.
Optimising the treatment for uncomplicated acute appendicitis (OPTIMA trial): a protocol for a multicentre, randomised, double-blinded placebo-controlled study

Introduction Emerging evidence has shown that an antibiotic first strategy is a viable treatment option for uncomplicated acute appendicitis (AA). Although there has recently been an interest and increase in the use of antibiotics as the primary strategy for treating uncomplicated AA, there is no consensus regarding the optimum antibiotic regimen. In particular, the long-term outcomes of different antibiotic regimens, such as the recurrence rate, still lack evidence. Given that the flora of the appendix is mainly anaerobic bacteria, we hypothesised that antianaerobe regimens could decrease the recurrence rate compared with those that did not include antianaerobic antibiotics. Methods and analysis The OPTIMA(Optimising the treatment for uncomplicated acute appendicitis) trial is a multicentre, double-blinded placebo-controlled superiority randomised study aimed to evaluate the role of antianaerobic antibiotics in the resolution of uncomplicated AA. Patients (18–65 years) with uncomplicated AA (without gangrenous, perforated appendicitis, appendiceal abscess, or appendiceal fecaliths) are eligible for inclusion. The primary endpoint of this study is the success rate of the treatment, defined as the resolution of AA resulting in discharge from the hospital without surgical intervention and recurrent symptoms within one year. Secondary endpoints include mortality, postintervention complications, recurrent symptoms up to one year after treatment, hospital stay, sick leave, treatment cost, pain symptom scores and quality of life. Data are reported as the number of cases (%), median (range) and relative risk, which will be analysed using the Mann-Whitney U test or χ2 test, as appropriate. P-value<0.05 will be considered significant. Ethics and dissemination The protocol has been approved by the Ethics Committee of Jinling Hospital on 13 November 2018 (2018NZKY-027-01). The trial findings will be published in peer-reviewed journals. Trial registration number ChiCTR1800018896.
Pathogenic variants of Valosin-containing protein induce lysosomal damage and transcriptional activation of autophagy regulators in neuronal cells

Mutations in the valosin‐containing protein (VCP) gene cause various lethal proteinopathies that mainly include inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) and amyotrophic lateral sclerosis (ALS). Different pathological mechanisms have been proposed. Here, we define the impact of VCP mutants on lysosomes and how cellular homeostasis is restored by inducing autophagy in the presence of lysosomal damage.
Lung adenocarcinoma manifesting as subsolid nodule potentially represents tumour in the equilibrium phase of immunoediting

Lung adenocarcinomas manifesting as subsolid nodules (SSN‐LUADs) possess distinct dormant behaviour. This study was designed to compare the immune landscapes of normal lungs (nLungs), SSN‐LUADs and LUADs manifesting as solid nodules (SN‐LUADs) so as to better understand the status of anti‐tumour immunity in SSN‐LUADs. Mass cytometry by time‐of‐flight analysis was performed on 299, 570 single cells from nLung, SSN‐LUAD and SN‐LUAD tissues. The immune cells were identified by phenotype, and the percentages of different immune cell subclusters were compared between SSN‐LUADs, SN‐LUADs and nLungs. Elevated percentage of CD8+ T cells were identified in SSN‐LUADs compared with in nLungs and SN‐LUADs. Elevated CD56bright NK cells and decreased CD56dim NK cells were identified in both SSN‐LUADs and SN‐LUADs compared with in nLungs. The immune landscape of SSN‐LUAD fits the theory of equilibrium phase of immunoediting, thus functional adaptive anti‐tumour immunity but impaired innate anti‐tumour immunity potentially contributes to the maintaining of its dormant behaviour.
Capacity Enhancement of Mobile Radio Networks Using Intermediate Relays

In infrastructure-based cellular wireless networks, mobile terminals communicate directly with their access point and the access point establishes global connectivity through the infrastructure network. When more terminals are squeezed into the network, there will be terminals transmitting simultaneously in the same frequency band causing interference in the network. In addition, remote terminals communicate with their access point using relatively high transmission power which cause interference to other transmitting terminals. Inevitably, the spectral efficiency and the maximum achievable capacity of the network is limited due to the ensuing interference. In this thesis, the relaying feature of terminals in ad hoc networks is adopted in the infrastructure-based cellular wireless network so that terminals can be used as intermediate relays to improve the capacity of the network. The rationale is that the intermediate terminals reduce the communication distance and allow higher data rates. The focus of this thesis is to first assess the potential benefit of the proposed network by separately studying the network performance limiting factors–the transmission power and interference– as transmission power limited and interference limited system. Based on these initial results, methods of increasing the network capacity are then developed: Terminals decide if they need an intermediate relay terminal to send their traffic, i.e., a routing problem is solved. A relaying terminal is selected with an optimal transmission power and rate after the relaying decision, i.e, transmission power and rate adaptation problem is solved. Different ways of fairly sharing the network resources are also suggested: The uniform slot size scheme, when terminals obtain equal share of the total TDMA frame, the uniform traffic size scheme, when terminals are allowed to send a uniform amount of data in slots of varying length and demand oriented scheme when terminals partially share the TDMA frame according to their traffic size and partially obtain an equal time share. The scheduling problem is thence solved to further improve the capacity. Furthermore, methods of using two or more frequencies within a cell, in addition to the cell’s primary frequency, are presented. These additional frequencies are used for relaying and are obtained by “recycling” from neighboring cells. As a result it is possible to achieve up to 60% increase in network capacity. And as the number of terminals increase, it is possible to achieve a per node throughput that will not actually go to zero but become a constant.
Outcomes of SARS-CoV-2 Infection in Unvaccinated Compared With Vaccinated Solid Organ Transplant Recipients: A Propensity Matched Cohort Study

Background. Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19). Vaccination may mitigate this risk; however, immunogenicity appears to be significantly impaired, with reports of increased risk of breakthrough infection. It is unknown if vaccine breakthrough infections are milder or as severe as infections in unvaccinated patients. Methods. We performed a multicenter matched cohort study between March 2020 and September 2021 to assess influence of COVID-19 vaccination on outcomes of COVID-19 infection. Treatment characteristics and disease severity outcomes were compared on the basis of vaccine status; breakthrough infections versus unvaccinated infections. Variable ratio propensity score matching based on age, sex, transplant type, and number of comorbidities, was used to develop the analytic cohort. Logistic regression was used to assess the influence of vaccination status on the selected outcomes. Results. From a cohort of 511 SOT patients with COVID-19, we matched 77 partially or fully vaccinated patients with 220 unvaccinated patients. Treatment characteristics including use of dexamethasone, remdesivir, and antibiotics did not differ. Vaccinated participants were more likely to receive tocilizumab, 15 of 77 (19.5%) versus 5 of 220 (2.3%), P < 0.001. Disease severity outcomes including oxygen requirement, mechanical ventilation, and mortality were similar among medically attended vaccine breakthroughs compared with unvaccinated patients. Conclusions. SOT recipients who develop medically attended COVID-19 following 1- or 2-dose vaccination seem to have similar disease severity to unvaccinated patients who develop infection. This is consistent with the requirement that SOT recipients need 3 or more vaccine doses and emphasizes the importance of alternate strategies for this population.
Chronic hepatitis B virus infection and the risk of hepatocellular carcinoma by age and country of origin in people living in Sweden: A national register study

Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), and surveillance is recommended for patients without cirrhosis when risk exceeds an incidence rate (IR) of 0.2%. Populations in Asia and sub‐Saharan Africa have been associated with HCC at younger ages, but the risk after immigration to Western countries should be investigated. The aim of this study was to study HCC by age and country of origin in people with chronic HBV infection in Sweden. Through national registers, residents with chronic HBV diagnosis (1990–2015) were identified with information on country of origin, immigration/emigration, death, coinfections, antiviral therapy, and HCC. Observation time started at HBV diagnosis, and IR and hazard ratios for HCC were calculated by sex, age, and region of origin. Among 16,410 individuals (47% women), the origin and observation time (person years) were as follows: Western Europe, 2316 (25,415); Eastern Europe, 2349 (26,237); Middle East/North Africa, 4402 (47,320); sub‐Saharan Africa, 3677 (30,565); Asia, 3537 (35,358); and other, 129 (1277). There were 232 individuals with HCC (82% in men). The IR increased with age and exceeded 0.2% for Asian men from age group 40–49 years (IR, 0.63; 95% confidence interval, 0.39–1.00), for men of other origins from age group 50–59 years, and for women aged ≥60 years originating from Eastern Europe, Asia, and Middle East/North Africa. After exclusion of patients with cirrhosis or HBV treatment, the IR still exceeded 0.2% in Asian men aged 40–49 years. This study demonstrates that HBV‐infected men of Asian origin should be recommended HCC surveillance at younger ages, but there is a need for further studies of HCC incidence in African‐born men without cirrhosis living in the Western world.
25-hydroxyvitamin D is a predictor of COVID-19 severity of hospitalized patients

Objectives Studies investigating the association between vitamin D and severity of COVID-19 have mixed results perhaps due to immunoassay assessment of total 25-hydroxyvitamin D (tD) (the sum of 25-hydroxyvitamin-D2 [25-OH-D2] and 25-hydroxyvitamin-D3 [25-OH-D3]). Liquid chromatography tandem mass spectrometry (LC-MS/MS) has high analytical specificity and sensitivity for 25-OH-D2 and 25-OH-D3, and thus enables a more accurate assessment of impact on COVID-19 outcomes. Methods We established reference intervals for 25-OH-D3 and tD using LC-MS/MS. 25-OH-D2, 25-OH-D3 and tD were quantitated for 88 COVID-19 positive and 122 COVID-19 negative specimens. Chi-square or Fisher’s exact tests were used to test associations in binary variables. T-Tests or Wilcoxon rank sum tests were used for continuous variables. Cox proportional hazards were used to test associations between 25-OH-D3 or tD levels and length of stay (LOS). For mortality and ventilation, logistic regression models were used. Results COVID-19 patients with deficient (<20 ng/mL) levels of 25-OH-D3 had significantly longer LOS by 15.3 days. COVID-19 P patients with deficient (<20 ng/mL) and insufficient (<30 ng/mL) of tD had significantly longer LOS by 12.1 and 8.2 days, respectively. Patients with insufficient levels of tD had significantly longer LOS by 13.7 days. COVID-19 patients with deficient serum 25-OH-D3 levels had significantly increased risk-adjusted odds of in-hospital mortality (OR [95% CI]: 5.29 [1.53–18.24]); those with insufficient 25-OH-D3 had significantly increased risk for requiring ventilation during hospitalization was found at LCMS insufficient cutoff (OR [95% CI]: 2.75 [1.10–6.90]). Conclusions There is an inverse relationship of 25-hydroxyvitamin D levels and hospital LOS for COVID-19 patients. Vitamin D status is a predictor for severity of outcomes. LCMS results are useful for assessing the odds of mortality and the need for ventilation during hospitalization.