The usefulness of randomized trials of lifestyle interventions for overweight, obesity, or metabolic syndrome: A systematic review.

BACKGROUND: Randomized controlled trials (RCTs) widely considered the gold standard for evidence-based healthcare may be limited in their clinical usefulness in lifestyle interventions for adults with overweight, obesity, or metabolic syndrome. OBJECTIVE: In this systematic review of lifestyle intervention RCTs we delineated trial usefulness. METHODS: Following prospective registration in PROSPERO (CRD4202347896), we conducted a comprehensive search across Medline, Scopus, Web of Science, and the Cochrane Library databases, covering the period from inception to December 2023. RCTs involving dietary interventions, with or without physical activity, and with or without behavioural support were included. Two reviewers independently performed study selection and data extraction. Study usefulness was assessed using a multidimensional 14 item questionnaire. Percentage compliance with usefulness items was computed. RESULTS: Of 1175 records, 30 RCTs (12,841 participants) were included. Among these, 13 (43%) RCTs complied with half of the usefulness items and only 3 (10%) complied with two-thirds of the items. For each usefulness item individually: 30 (100%) reported the burden of the problem addressed, 15 (50%) contextualized the trial through a systematic review, 18 (60%) presented an informative trial with clinically meaningful outcomes evaluated at a stated statistical power, 17 (57%) had low risk of bias, 2 (7%) exhibited pragmatic features pertaining to the trial methodologies and outcomes relevant to real-world application.18 (60%) were patient centred with formal patient involvement, none (0%) demonstrated value for money, 17 (57%) were completed according to their feasibility assessment achieving at least 90% of the estimated sample size, and 30 (100%) reported at least one of five transparency or openness features. CONCLUSION: Only one in 10 lifestyle RCTs met two-thirds of the usefulness features. It is imperative to meet these criteria when devising future trials within the field of nutrition to reduce research waste.

Production Technologies for Recombinant Antibodies: Insights into Eukaryotic, Prokaryotic, and Transgenic Expression Systems.

Recombinant antibodies, a prominent class of recombinant proteins, are witnessing substantial growth in research and diagnostics. Recombinant antibodies are being produced employing diverse hosts ranging from highly complex eukaryotes, for instance, mammalian cell lines (and insects, fungi, yeast, etc.) to unicellular prokaryotic models like gram-positive and gram-negative bacteria. This review delves into these production methods, highlighting approaches like antibody phage display that employs bacteriophages for gene library creation. Recent studies emphasize monoclonal antibody generation through hybridoma technology, utilizing hybridoma cells from myeloma and B-lymphocytes. Transgenic plants and animals have emerged as sources for polyclonal and monoclonal antibodies, with transgenic animals preferred due to their human-like post-translational modifications and reduced immunogenicity risk. Chloroplast expression offers environmental safety by preventing transgene contamination in pollen. Diverse production technologies, such as stable cell pools and clonal cell lines, are available, followed by purification via techniques like affinity chromatography. The burgeoning applications of recombinant antibodies in medicine have led to their large-scale industrial production.

Metallic nanoentities: Bio-engineered silver, gold, and silver/gold bimetallic nanoparticles for biomedical applications.

This present study reports the biogenic synthesis of silver nanoparticles (AgNPs), gold nanoparticles (AuNPs) and Ag/Au bimetallic nanoparticles (BNPs) using bark extract of plant Tamarix aphylla (T.A). The bark extract contained total polyphenolic compounds and total flavonoids as 0.0362 mg/mg and 0.2928 mg/mg of the dried bark extract respectively. Silver nitrate (AgNO3) and hydrogen tetra chloroaurate trihydrate (HAuCl4.3H2O) were used as precursors while deionised water and methanol (CH3OH) were used as solvents. Synthesized nanoparticles were characterized through UV-visible spectroscopy, SEM (scanning electron microscopy), TEM (transmission electron microscopy) and FTIR (Fourier transform infrared) for their morphology, structure, and identification of different functional groups. The UV-visible spectra of AgNPs, AuNPs and Ag/Au BNPs showed peaks at 436, 532 and 527 nm respectively due to the excitation of Surface Plasmon Resonance. SEM and TEM images showed spherical and well distributed nanoparticles (NPs) with particle size as 29 nm (AgNPs), 13 nm (AuNPs) and 26 nm (Ag/Au BNPs). The synthesized NPs are significantly active against inhibition of free radicals, α-amylase, α-glucosidase and have anti inflammatory potential with AgNPs having the highest percent activity at 400 µg/ml, followed by Ag/Au BNPs. The same trend (AgNPs > Ag/AuBNPs > AuNPs) has been observed at all concentrations i.e. 100 µg/ml, 200 µg/ml and 400 µg/ml. AuNPs have shown lowest activity at all concentrations. So the current study strongly confirms use of T.A bark extract as reducing agent for synthesis of metal NPs and opens up a new possibility of using these green synthesized NPs as biomedicines. We also suggest further in vivo investigation to report any side effects if present.

Anti-Acanthamoebic effects of silver-conjugated tetrazole nanoparticle.

Tetrazoles are five-membered ring aromatic heterocyclic molecules that consist of one carbon and four nitrogen atoms. Several tetrazole-based drugs have shown promising activities against bacteria, fungi, asthma, cancer, hypertension etc. The overall aim of this study was to determine anti-Acanthamoebic properties of tetrazoles and tetrazole-conjugated silver nanoparticles. Tetrazole-conjugated silver nanoparticles were synthesized and confirmed using ultraviolet-visible spectrometry, Dynamic light scattering, and Fourier-transform infrared spectroscopy. Using amoebicidal, encystment, and excystment assays, the findings revealed that tetrazoles exhibited antiamoebic properties and these effects were enhanced when conjugated with silver nanoparticles. Importantly, conjugation with silver nanoparticles inhibited parasite-mediated human cell death in vitro, as measured by lactate dehydrogenase release, but it reduced toxic effects of drugs alone on human cells. Overall, these results showed clearly that tetrazoles exhibit potent antiamoebic properties which can be enhanced by conjugation with silver nanoparticles and these potential in the rational development of therapeutic interventions against parasitic infections such as keratitis and granulomatous amoebic encephalitis due to pathogenic Acanthamoeba.

Unveiling the uncommon: Giant internal jugular vein aneurysm in a neurofibromatosis patient: A case report.

Neurofibromatosis Type 1 (NF1) is a rare autosomal dominant disorder that has a wide array of clinical manifestations. NF1 Vasculopathies constitute 0.4% to 6.4% of the findings and they often develop in the arterial circulation while venous involvement is rare. We present a case of a 73-year-old male with NF1 with an incidental finding of right neck swelling for 2 months. Different radiological modalities were performed, identifying the lesion as an internal jugular vein aneurysm. The patient was managed conservatively as he was asymptomatic in relation to the swelling. NF1 venous vasculopathies are rare but they have detrimental consequences such as rupture and severe hemorrhage in view of the fragility of the aneurysmal wall and the infiltration of the neurofibroma into the vessel. Hence, high clinical suspicion and selective imaging and follow-up is advisable for physicians.

Assessment of image quality and establishment of local acceptable quality dose for computed tomography based on patient effective diameter.

Purpose: We aim to develop modified clinical indication (CI)-based image quality scoring criteria (IQSC) for assessing image quality (IQ) and establishing acceptable quality doses (AQDs) in adult computed tomography (CT) examinations, based on CIs and patient sizes. Approach: CT images, volume CT dose index ( CTDI vol ), and dose length product (DLP) were collected retrospectively between September 2020 and September 2021 for eight common CIs from two CT scanners at a central hospital in the Kingdom of Bahrain. Using the modified CI-based IQSC and a Likert scale (0 to 4), three radiologists assessed the IQ of each examination. AQDs were then established as the median value of CTDI vol and DLP for images with an average score of 3 and compared to national diagnostic reference levels (NDRLs). Results: Out of 581 examinations, 60 were excluded from the study due to average scores above or below 3. The established AQDs were lower than the NDRLs for all CIs, except AQDs / CTDI vol for oncologic follow-up for large patients (28 versus 26 mGy) in scanner A, besides abdominal pain for medium patients (16 versus 15 mGy) and large patients (34 versus 27 mGy), and diverticulitis/appendicitis for medium patients (15 versus 12 mGy) and large patients (33 versus 30 mGy) in scanner B, indicating the need for optimization. Conclusions: CI-based IQSC is crucial for IQ assessment and establishing AQDs according to patient size. It identifies stations requiring optimization of patient radiation exposure.

A novel homozygous missense TTC12 variant identified in an infertile Pakistani man with severe oligoasthenoteratozoospermia and primary ciliary dyskinesia.

TTC12 is a cytoplasmic and centromere-localized protein that plays a role in the proper assembly of dynein arm complexes in motile cilia in both respiratory cells and sperm flagella. This finding underscores its significance in cellular motility and function. However, the wide role of TTC12 in human spermatogenesis-associated primary ciliary dyskinesia (PCD) still needs to be elucidated. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify potentially pathogenic variants causing PCD and multiple morphological abnormalities of sperm flagella (MMAF) in an infertile Pakistani man. Diagnostic imaging techniques were used for PCD screening in the patient. Real-time polymerase chain reaction (RT‒PCR) was performed to detect the effect of mutations on the mRNA abundance of the affected genes. Papanicolaou staining and scanning electron microscopy (SEM) were carried out to examine sperm morphology. Transmission electron microscopy (TEM) was performed to examine the ultrastructure of the sperm flagella, and the results were confirmed by immunofluorescence staining. Using WES and Sanger sequencing, a novel homozygous missense variant (c.C1069T; p.Arg357Trp) in TTC12 was identified in a patient from a consanguineous family. A computed tomography scan of the paranasal sinuses confirmed the symptoms of the PCD. RT-PCR showed a decrease in TTC12 mRNA in the patient's sperm sample. Papanicolaou staining, SEM, and TEM analysis revealed a significant change in shape and a disorganized axonemal structure in the sperm flagella of the patient. Immunostaining assays revealed that TTC12 is distributed throughout the flagella and is predominantly concentrated in the midpiece in normal spermatozoa. In contrast, spermatozoa from patient deficient in TTC12 showed minimal staining intensity for TTC12 or DNAH17 (outer dynein arms components). This could lead to MMAF and result in male infertility. This novel TTC12 variant not only illuminates the underlying genetic causes of male infertility but also paves the way for potential treatments targeting these genetic factors. This study represents a significant advancement in understanding the genetic basis of PCD-related infertility.

Evaluation of pediatric patients for intestinal transplantation in the modern era.

OBJECTIVES: To review recent evaluations of pediatric patients with intestinal failure (IF) for intestinal transplantation (ITx), waiting list decisions, and outcomes of patients listed and not listed for ITx at our center. METHODS: Retrospective chart review of 97 patients evaluated for ITx from January 2014 to December 2021 including data from referring institutions and protocol laboratory testing, body imaging, endoscopy, and liver biopsy in selected cases. Survival analysis used Kaplan-Meier estimates and Cox proportional hazards regression. RESULTS: Patients were referred almost entirely from outside institutions, one-third because of intestinal failure-associated liver disease (IFALD), two-thirds because of repeated infective and non-IFALD complications under minimally successful intestinal rehabilitation, and a single patient because of lost central vein access. The majority had short bowel syndrome (SBS). Waiting list placement was offered to 67 (69%) patients, 40 of whom for IFALD. The IFALD group was generally younger and more likely to have SBS, have received more parenteral nutrition, have demonstrated more evidence of chronic inflammation and have inferior kidney function compared to those offered ITx for non-IFALD complications and those not listed. ITx was performed in 53 patients. Superior postevaluation survival was independently associated with higher serum creatinine (hazard ratio [HR] 15.410, p = 014), whereas inferior postevaluation survival was associated with ITx (HR 0.515, p = 0.035) and higher serum fibrinogen (HR 0.994, p = 0.005). CONCLUSIONS: Despite recent improvements in IF management, IFALD remains a prominent reason for ITx referral. Complications of IF inherent to ITx candidacy influence postevaluation and post-ITx survival.

Analyzing the impact of pesticides on the indus river: contamination levels in water, sediment, fish, and associated human health risks.

Pesticides are frequently used to protect crop yields and manage malaria vectors; however, their inadvertent transport into aquatic habitats poses a significant concern. Various anthropogenic activities influence the Indus River in Pakistan. This study aimed to assess the presence of eight pesticide residues at three different sites (Kalabagh, Kundian, and Chashma) in water, sediment, and the fish species (Labeo rohita) during both dry and wet seasons to measure the intensity of this pressure. Pesticide analysis was carried out using gas chromatography equipped with an electron capture detector. The results revealed the highest concentrations of pesticides during both dry and wet seasons at all sites, measuring 0.83 and 0.62 µg/l (water), 12.37 and 9.20 µg/g/dw (sediment), and 14.27 and 11.29 µg/g/ww (L. rohita), respectively. Overall, pesticide concentrations were higher in the dry season than in the wet season across all study sites. Based on detection frequency and concentration in both seasons at all sites, dominant pesticides included cypermethrin and carbofuran (in water), as well as endosulfan and cypermethrin (in sediment and fish tissue). Levels of endosulfan and cypermethrin exceeded standard limits. Moreover, principal component analysis (PCA) indicated no correlation among pesticides in fish tissue, sediment, and water. However, pesticides exhibited different behavior in different seasons. Furthermore, endosulfan and triazophos impose great human health risk, as indicated by the THQ value (> 1). The overall HI value was greater for site 1 in the dry season (8.378). The study concluded that the presence of agricultural pesticides in the Indus River poses a risk to aquatic life and has the potential to disrupt the entire food chain. This highlights the importance of sustainable practices for the study area and Pakistan overall agricultural and environmental sustainability. It is further recommended to strengthen regulations for reduced pesticide use and promote eco-friendly pest management.

Suppressor T helper type 17 cell responses in intestinal transplant recipients with allograft rejection.

BACKGROUND: Intestinal transplant (ITx) rejection is associated with memory T helper type 17 cell (Th17) infiltration of grafted tissues. Modulation of Th17 effector cell response is facilitated by T regulatory (Treg) cells, but a phenotypic characterization of this process is lacking in the context of allograft rejection. METHODS: Flow cytometry was performed to examine the expression of surface receptors, cytokines, and transcription factors in Th17 and Treg cells in ITx control (n = 34) and rejection patients (n = 23). To elucidate key pathways guiding the rejection biology, we utilized RNA sequencing (RNAseq) and assessed epigenetic stability through pyrosequencing of the Treg-specific demethylated region (TSDR). RESULTS: We found that intestinal allograft rejection is characterized by Treg cellular infiltrates, which are polarized toward Th17-type chemokine receptor, ROR-γt transcription factor expression, and cytokine production. These Treg cell subsets have maintained epigenetic stability, as defined by FoxP3-TSDR methylation status, but displayed upregulation of functional Treg and purinergic signaling genes by RNAseq analysis such as CD39, in keeping with suppressor Th17 properties. CONCLUSION: We show that ITx rejection is associated with increased polarized cells that express a Th17-like phenotype concurrent with regulatory purinergic markers.

Exploring the effect of different application rates of biochar on the accumulation of nutrients and growth of flue-cured tobacco (Nicotiana tabacum).

Background: Biochar application has become one of the most potential tools to improve soil fertility and plant growth for sustainable and eco-friendly agriculture. However, both positive and negative effects of biochar application have been recorded on plant growth and soil fertility. Methods: This study investigated the impact of different application rates (0, 600, 900, 1200, and 1800 kg/ha) of biochar on the soil nutrient contents, accumulation of nutrients and dry matter in different plant parts, and growth of flue-cured tobacco plants under field conditions. Results: Results demonstrated that soil organic carbon pool and carbon/nitrogen ratio were increased proportionally with the increasing dosage of biochar, 25.54 g/kg and 14.07 g/kg compared with control 17 g/kg and 10.13 g/kg, respectively. The contents of soil total nitrogen were also significantly increased after biochar application in the middle (1.77 g/kg) and late-growth (1.54 g/kg) stages of flue-cured tobacco than in control (1.60 g/kg and 1.41 g/kg, respectively). The contents of soil nitrate nitrogen were also higher under low (600 and 900 kg/ha) application rates of biochar and reduced when higher (1200 and 1800 kg/ha) dosages of biochar were applied. However, it was observed that varying application rates of biochar had no impact on soil ammonium nitrogen content during the growth period of flue-cured tobacco plants. The nutrient accumulation (N, P, K) in different parts of flue-cured tobacco plants was significantly increased under a low application rate of biochar, which enhanced the soil and plant analyzer development values, effective leaves number, growth, dry matter accumulation, and leaf yield of flue-cured tobacco. In contrast, the high biochar application rate (1200 and 1800 kg/ha) negatively impacted nutrient accumulation and growth of flue-cured tobacco. Conclusion: Conclusively, the optimum application of biochar (600 and 900 kg/ha) is beneficial for plant growth, soil fertility, accumulation of nutrients, and dry matter in different plant parts. However, excessive biochar application (> 900 kg/ha) could inhibit flue-cured tobacco plant growth. This study provides a theoretical foundation for biochar application in tobacco and other crop production to obtain agricultural sustainability and economic stability.

Cereal sprout-based food products: Industrial application, novel extraction, consumer acceptance, antioxidant potential, sensory evaluation, and health perspective.

Cereal grains are a good source of macronutrients and micronutrients that are required for metabolic activity in the human body. Sprouts have been studied to enhance the nutrient profile. Moreover, secondary metabolites are examined as green food engineering technology that is used in the pharmaceutical, functional ingredients, nutraceutical, and cosmetic industries. The sprout-based food is commonly used to enhance the quality of products by softening the structure of the whole grain and increasing the phytochemicals (nutritional value and bioactive compounds). These sprouting grains can be added to a variety of products including snacks, bakery, beverage, and meat. Consuming whole grains has been shown to reduce the incidence and mortality of a variety of chronic and noncommunicable diseases. Sprouting grains have a diversity of biological functions, including antidiabetic, antioxidant, and anticancer properties. Cereal sprout-based products are more beneficial in reducing the risk of cardiovascular diseases and gastrointestinal tract diseases. The novel extraction techniques (microwave-existed extraction, pulse electric field, and enzyme-associated) are applied to maintain and ensure the efficiency, safety, and nutritional profile of sprout. Nutrient-dense sprouts have a low environmental impact and are widely accepted by consumers. This review explores for the first time and sheds light on the antioxidant potential, sensory evaluation, industrial applications, and health perspective of cereal sprout-based food products.

Oxadiazole Derivatives of Diclofenac as an Anti-proliferative Agent for B-cell Non-Hodgkin Lymphoma: An In vitro and In Silico Studies.

BACKGROUND: Non-Hodgkin lymphoma of B cell origin is the common type of lymphoma- related malignancy with poor response rate with conventional front-line therapies. AIM: The aim of the present study was to investigate the potential of new anti-inflammatory oxadiazole derivatives of Diclofenac as an anti-lymphoma agent through in vitro and in silico approaches. METHODS: Anti-lymphoma potential was evaluated by alamar blue technique. MTT assay employed for cytotoxicity. Gene and protein expression studies was performed by qRT-PCR and ELISA respectively. Docking studies was performed by using MOE program. RESULTS: Among five diclofenac derivatives, (II) showed promising anti-lymphoma effects, where it inhibited the expression of BCL-2, p-38 MAPK and TGF-ß in both follicular and Burkitt's lymphoma cells and was non-toxic against normal human fibroblast cells. The in silico studies against BCL-2 revealed that the unsubstituted Sulphur group in (II) is involved in the crucial interactions with the binding site residue. CONCLUSION: The compound (II) can be a potential therapeutic candidate for B-cell non-Hodgkin lymphoma and deserves further development as a novel anti-lymphoma agent.

Potential anti-amoebic effects of synthetic 1,4-benzothiazine derivatives against Acanthamoeba castellanii.

A rare but lethal central nervous system disease known as granulomatous amoebic encephalitis (GAE) and potentially blinding Acanthamoeba keratitis are diseases caused by free-living Acanthamoeba. Currently, no therapeutic agent can completely eradicate or prevent GAE. Synthetic compounds are a likely source of bioactive compounds for developing new drugs. This study synthesized seventeen 1,4-benzothiazine derivatives (I -XVII) by a base-catalyzed one-pot reaction of 2-amino thiophenol with substituted bromo acetophenones. Different spectroscopic techniques, such as EI-MS, 1H-, and 13C NMR (only for the new compounds), were used for the structural characterization and conformation of compounds. These compounds were assessed for the first time against Acanthamoeba castellanii. All compounds showed anti-amoebic potential in vitro against A. castellanii, reducing its ability to encyst and excyst at 100 µM. Compounds IX, X, and XVI showed the most potent activities among all derivatives and significantly reduced the viability to 5.3 × 104 (p < 0.0003), 2 × 105 (p < 0.006), and 2.4 × 105 (p < 0.002) cells/mL, respectively. The cytotoxicity profile revealed that these molecules showed lower to moderate cytotoxicity, i.e., 36 %, 2 %, and 21 %, respectively, against human keratinocytes in vitro. These results indicate that 1,4-benzothiazines showed potent in vitro activity against trophozoites and cysts of A. castellanii. Hence, these 1,4-benzothiazine derivatives should be considered to develop new potential therapeutic agents against Acanthamoeba infections.

Computational analysis of bevacizumab binding with protein receptors for its potential anticancer activity.

Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments. In this study, we investigated the binding free energy (ΔG) of bevacizumab, an anti-cancer therapy targeting angiogenesis through the inhibition of vascular endothelial growth factor (VEGF), with various proto-oncogenes including CDK4, EGFR, frizzled, IGFR, OmoMYC, and KIT. Our in-silico investigation revealed that hydrogen bonding is pivotal in inducing conformational changes within the DNA structure, impeding its replication and preventing cell death. Molecular docking results revealed the presence of crucial hydrogen bonds and supported the formation of stable bevacizumab complexes. The molecular docking scores for the tested complexes were CDK4 (Score = -7.2 kcal/mol), EGFR (Score = -8.5 kcal/mol), frizzled (Score = -6.9 kcal/mol), IGFR (Score = -7.8 kcal/mol), KIT (Score = -6.5 kcal/mol), and MYC (Score = -8.3 kcal/mol). The binding mode demonstrated vital hydrogen bonds correlated with the observed energy gap. Notably, the calculated binding free energies of the tested compounds are as follows: CDK4 (ΔG = 24275.195 ± 6411.293 kJ/mol), EGFR (ΔG = 363273.625 ± 8731.466 kJ/mol), frizzled (ΔG = 181751.990 ± 28438.515 kJ/mol), IGFR (ΔG = 162414.725 ± 10728.367 kJ/mol), KIT (ΔG = 40162.585 ± 4331.017 kJ/mol), and MYC (ΔG = 434783.463 ± 53989.676 kJ/mol). Furthermore, through extensive 100 ns MD simulations, we observed the formation of a stable bevacizumab complex structure. The simulations confirmed the stability of the bevacizumab complex with the proto-oncogenes. The results of this study highlight the potential of bevacizumab complex as a promising candidate for anticancer treatment. The identification of hydrogen bonding, along with the calculated binding free energies and molecular docking scores, provides valuable insights into the molecular interactions and stability of the bevacizumab complexes. These findings and the extensive MD simulations open new avenues for future research and development of bevacizumab as a targeted therapy for breast cancer and other related malignancies.Communicated by Ramaswamy H. Sarma.

Lactase can target cellular differentiation of Acanthamoeba castellanii belonging to the T4 genotype.

The free living Acanthamoeba spp. are ubiquitous amoebae associated with potentially blinding disease known as Acanthamoeba keratitis (AK) and a fatal central nervous system infection granulomatous amoebic encephalitis (GAE). With the inherent ability of cellular differentiation, it can phenotypically transform to a dormant cyst form from an active trophozoite form. Acanthamoeba cysts are highly resistant to therapeutic agents as well as contact lens cleaning solutions. One way to tackle drug resistance against Acanthamoeba is by inhibiting the formation of cysts from trophozoites. The biochemical analysis showed that the major component of Acanthamoeba cyst wall is composed of carbohydrate moieties such as galactose and glucose. The disaccharide of galactose and glucose is lactose. In this study, we analyzed the potential of lactase enzyme to target carbohydrate moieties of cyst walls. Amoebicidal assessment showed that lactase was ineffective against trophozoite of A. castellanii but enhanced amoebicidal effects of chlorhexidine. The lactase enzyme did not show any toxicity against normal human keratinocyte cells (HaCaT) at the tested range. Hence, lactase can be used for further assessment for development of potential therapeutic agents in the management of Acanthamoeba infection as well as formulation of effective contact lens disinfectants.

Current Advances in Graft-versus-host Disease After Intestinal Transplantation.

Graft-versus-host disease (GvHD) remains a potentially fatal complication following intestinal transplant (ITx). Over the past decade, advances in the understanding of the pathophysiology of this complex immunological phenomenon have led to the reassessment of the host systemic immune response and have created a gateway for novel preventive and therapeutic strategies. Although sufficient evidence dictates the use of corticosteroids as a first-line option, the treatment for refractory disease remains contentious and lacks a standardized therapeutic approach. Timely diagnosis remains crucial, and the advent of chimerism detection and immunological biomarkers have transformed the identification, prognostication, and potential for survival after GvHD in ITx. The objectives of the following review aim to discuss the clinical and diagnostic features, pathophysiology, advances in immune biomarkers, as well as therapeutic opportunities in the prevention and treatment of GvHD in ITx.

Aluminum phytotoxicity in acidic environments: A comprehensive review of plant tolerance and adaptation strategies.

Aluminum (Al), a non-essential metal for plant growth, exerts significant phytotoxic effects, particularly on root growth. Anthropogenic activities would intensify Al's toxic effects by releasing Al3+ into the soil solution, especially in acidic soils with a pH lower than 5.5 and rich mineral content. The severity of Al-induced phytotoxicity varies based on factors such as Al concentration, ionic form, plant species, and growth stages. Al toxicity leads to inhibited root and shoot growth, reduced plant biomass, disrupted water uptake causing nutritional imbalance, and adverse alterations in physiological, biochemical, and molecular processes. These effects collectively lead to diminished plant yield and quality, along with reduced soil fertility. Plants employ various mechanisms to counter Al toxicity under stress conditions, including sequestering Al in vacuoles, exuding organic acids (OAs) like citrate, oxalate, and malate from root tip cells to form Al-complexes, activating antioxidative enzymes, and overexpressing Al-stress regulatory genes. Recent advancements focus on enhancing the exudation of OAs to prevent Al from entering the plant, and developing Al-tolerant varieties. Gene transporter families, such as ATP-Binding Cassette (ABC), Aluminum-activated Malate Transporter (ALMT), Natural resistance-associated macrophage protein (Nramp), Multidrug and Toxic compounds Extrusion (MATE), and aquaporin, play a crucial role in regulating Al toxicity. This comprehensive review examined recent progress in understanding the cytotoxic impact of Al on plants at the cellular and molecular levels. Diverse strategies developed by both plants and scientists to mitigate Al-induced phytotoxicity were discussed. Furthermore, the review explored recent genomic developments, identifying candidate genes responsible for OAs exudation, and delved into genome-mediated breeding initiatives, isolating transgenic and advanced breeding lines to cultivate Al-tolerant plants.

Co-metabolic degradation and metabolite detection of hexabromocyclododecane by Shewanella oneidensis MR-1.

Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant; however, it is a persistent organic pollutant as well as affects the human thyroid hormones and causes cancer. However, the degradation of HBCD has received little attention from researchers. Due to its bioaccumulative and hazardous properties, an appropriate strategy for its remediation is required. In this study, we investigated the biodegradation of HBCD using Shewanella oneidensis MR-1 under optimized conditions. The Box-Behnken design (BBD) was implemented for the optimization of the physical degradation parameters of HBCD. S. oneidensis MR-1 showed the best degradation performance at a temperature of 30 °C, pH 7, and agitation speed of 115 rpm, with an HBCD concentration of 1125 µg/L in mineral salt medium (MSM). The strain tolerated up to 2000 µg/L HBCD. Gas chromatography-mass spectrometry analysis identified three intermediates, including 2-bromo dodecane, 2,7,10-trimethyldodecane, and 4-methyl-1-decene. The results provide an insightful understanding of the biodegradation of HBCD by S. oneidensis MR-1 under optimized conditions and could pave the way for further eco-friendly applications. KEY POINTS: • HBCD biodegradation by Shewanella oneidensis • Optimization of HBCD biodegradation by the Box-Behnken analysis • Identification of useful metabolites from HBCD degradation.

BIR: Biomedical Information Retrieval System for Cancer Treatment in Electronic Health Record Using Transformers.

The rapid growth of electronic health records (EHRs) has led to unprecedented biomedical data. Clinician access to the latest patient information can improve the quality of healthcare. However, clinicians have difficulty finding information quickly and easily due to the sheer data mining volume. Biomedical information retrieval (BIR) systems can help clinicians find the information required by automatically searching EHRs and returning relevant results. However, traditional BIR systems cannot understand the complex relationships between EHR entities. Transformers are a new type of neural network that is very effective for natural language processing (NLP) tasks. As a result, transformers are well suited for tasks such as machine translation and text summarization. In this paper, we propose a new BIR system for EHRs that uses transformers for predicting cancer treatment from EHR. Our system can understand the complex relationships between the different entities in an EHR, which allows it to return more relevant results to clinicians. We evaluated our system on a dataset of EHRs and found that it outperformed state-of-the-art BIR systems on various tasks, including medical question answering and information extraction. Our results show that Transformers are a promising approach for BIR in EHRs, reaching an accuracy and an F1-score of 86.46%, and 0.8157, respectively. We believe that our system can help clinicians find the information they need more quickly and easily, leading to improved patient care.