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Abstract Background Technology-enabled services (TES; clinical services that include both technology-driven [e.g., personal sensing technologies] and person-powered support elements) may address gaps in depression and anxiety treatments in healthcare settings. The current study: (1) developed a TES tailored for Primary Care patients with depression and/or anxiety, and (2) conducted a pilot randomized controlled trial to assess the efficacy of the TES compared to a digital psychoeducation control app. Methods Participants were randomized to either: (1) TES: the “Vira” smartphone app (Ksana Health Inc.), informed by behavioral activation and using passive sensing technology to provide behavioral “insights” and target behaviors associated with mental health symptoms, alongside lay-provider coaching, or (2) Control: the Mood Education mobile app (ME), containing static psychoeducational resources designed to target mental health symptoms. Both apps collected usage data. Participants completed assessments on depression (PHQ-9), anxiety (GAD-7), health-related quality of life (PedsQL), and engagement (TWEETs) at baseline, mid-treatment (week 4), end-of-treatment (week 8), and post-treatment (week 12). Results Participants (N = 130) were randomized to receive either the TES (Vira; Mage= 30) or ME (Mage= 33). Linear mixed-effects models determined significant improvements in PHQ-9 and GAD-7 scores for participants across both conditions (ps

In the United States in 2021, an outbreak of 4 cases of Burkholderia pseudomallei, the etiologic agent of melioidosis and a Tier One Select Agent (potential for deliberate misuse and subsequent harm), resulted in 2 deaths. The causative strain, B. pseudomallei ATS2021, was unintentionally imported into the United States in an aromatherapy spray manufactured in India. We established that ATS2021 represents a virulent strain of B. pseudomallei capable of robust formation of biofilm at physiologic temperatures that may contribute to virulence. By using mouse melioidosis models, we determined median lethal dose estimates and analyzed the bacteriologic and histopathologic characteristics of the organism, particularly the potential neurologic pathogenesis that is probably associated with the bimABm allele identified in B. pseudomallei strain ATS2021. Our data, combined with previous case reports and the identification of endemic B. pseudomallei strains in Mississippi, support the concept that melioidosis is emerging in the United States.

Abstract Our group previously showed that genetic or pharmacological inhibition of the cystine/glutamate antiporter, system xc−, mitigates excitotoxicity after anoxia by increasing latency to anoxic depolarization, thus attenuating the ischaemic core. Hypoxia, however, which prevails in the ischaemic penumbra, is a condition where neurotransmission is altered, but excitotoxicity is not triggered. The present study employed mild hypoxia to further probe ischaemia‐induced changes in neuronal responsiveness from wild‐type and xCT KO (xCT−/−) mice. Synaptic transmission was monitored in hippocampal slices from both genotypes before, during and after a hypoxic episode. Although wild‐type and xCT−/− slices showed equal suppression of synaptic transmission during hypoxia, mutant slices exhibited a persistent potentiation upon re‐oxygenation, an effect we termed ‘post‐hypoxic long‐term potentiation (LTP)’. Blocking synaptic suppression during hypoxia by antagonizing adenosine A1 receptors did not preclude post‐hypoxic LTP. Further examination of the induction and expression mechanisms of this plasticity revealed that post‐hypoxic LTP was driven by NMDA receptor activation, as well as increased calcium influx, with no change in paired‐pulse facilitation. Hence, the observed phenomenon engaged similar mechanisms as classical LTP. This was a remarkable finding as theta‐burst stimulation‐induced LTP was equivalent between genotypes. Importantly, post‐hypoxic LTP was generated in wild‐type slices pretreated with system xc− inhibitor, S‐4‐carboxyphenylglycine, thereby confirming the antiporter's role in this phenomenon. Collectively, these data indicate that system xc− interference enables neuroplasticity in response to mild hypoxia, and, together with its regulation of cellular damage in the ischaemic core, suggest a role for the antiporter in post‐ischaemic recovery of the penumbra.

Abstract Post‐exercise hot (HWI) and cold (CWI) water immersion are popular strategies used by athletes in a range of sporting contexts, such as enhancing recovery or adaptation. However, prolonged heating bouts increase neuroendocrine responses that are associated with perceptions of fatigue. Fourteen endurance‐trained runners performed three trials consisting of two 45‐min runs at 95% lactate threshold on a treadmill separated by 6 h of recovery. Following the first run, participants completed one of HWI (30 min, 40°C), CWI (15 min, 14°C) or control (CON, 30 min rest in ambient conditions) in a randomised order. Perceived effort and recovery were measured using ratings of perceived exertion (RPE) and the Acute Recovery and Stress Scale (ARSS), whilst physiological responses including venous concentrations of a range of neuroendocrine markers, superficial femoral blood flow, heart rate and rectal temperature were measured. Exercise increased neuroendocrine responses of interleukin‐6, adrenaline and noradrenaline (all P 0.05), nor RPE (P = 0.68), despite differences in rectal temperature, superficial femoral blood flow following the first run, and participants’ expected recovery prior to the intervention (all P

Abstract How prostate cancer cells and their precursors mediate changes in the tumor microenvironment (TME) to drive prostate cancer progression is unclear, in part due to the inability to longitudinally study the disease evolution in human tissues. To overcome this limitation, we perform extensive single-cell RNA-sequencing (scRNA-seq) and molecular pathology of the comparative biology between human prostate cancer and key stages in the disease evolution of a genetically engineered mouse model (GEMM) of prostate cancer. Our studies of human tissues reveal that cancer cell-intrinsic activation of MYC signaling is a common denominator across the well-known molecular and pathological heterogeneity of human prostate cancer. Cell communication network and pathway analyses in GEMMs show that MYC oncogene-expressing neoplastic cells, directly and indirectly, reprogram the TME during carcinogenesis, leading to a convergence of cell state alterations in neighboring epithelial, immune, and fibroblast cell types that parallel key findings in human prostate cancer.

Abstract Many archetypal and emerging classes of small-molecule therapeutics form covalent protein adducts. In vivo, both the resulting conjugates and their off-target side-conjugates have the potential to elicit antibodies, with implications for allergy and drug sequestration. Although β-lactam antibiotics are a drug class long associated with these immunological phenomena, the molecular underpinnings of off-target drug-protein conjugation and consequent drug-specific immune responses remain incomplete. Here, using the classical β-lactam penicillin G (PenG), we probe the B and T cell determinants of drug-specific IgG responses to such conjugates in mice. Deep B cell clonotyping reveals a dominant murine clonal antibody class encompassing phylogenetically-related IGHV1, IGHV5 and IGHV10 subgroup gene segments. Protein NMR and x-ray structural analyses reveal that these drive structurally convergent binding modes in adduct-specific antibody clones. Their common primary recognition mechanisms of the penicillin side-chain moiety (phenylacetamide in PenG)—regardless of CDRH3 length—limits cross-reactivity against other β-lactam antibiotics. This immunogenetics-guided discovery of the limited binding solutions available to antibodies against side products of an archetypal covalent inhibitor now suggests future potential strategies for the ‘germline-guided reverse engineering’ of such drugs away from unwanted immune responses.

A mechanism for energy transfer from the solar wind to the Martian ionosphere through open magnetic flux rope is proposed based on the observations by Mars Atmosphere and Volatile EvolutioN (MAVEN). The satellite was located in the dayside magnetosheath at an altitude of about 700 km above the northern hemisphere. Collisions between the hot solar wind protons and the cold heavy ions/neutrals in the subsolar region can cool the protons and heat the heavy ions. As a result, the magnetosheath protons are siphoned into the ionosphere due to the thermal pressure gradient of protons and the heated heavy ions escape along the open magnetic field lines. Although direct collisions in the lower-altitude region were not detected, this physical process is demonstrated by MAVEN measurements of enhanced proton density, decreased proton temperature and oppositely directed motions of hot and cool protons within the flux rope, which are very different from the observational features of the flux transfer events near the Earth’s magnetopause. This mechanism could universally exist in many contexts where a collisionless plasma region is connected to a collisional plasma region. By reconstructing the magnetic geometry and the cross-section of the flux rope using the Grad-Shafranov technique, the ion loss rates are quantitatively estimated to be on the order of 1023 s−1, which is much higher than previously estimated.

Abstract Wide-scale sensing of natural and human-made events is critical for protecting against environmental disasters and reducing the monetary losses associated with telecommunication service downtime. However, achieving dense sensing coverage is difficult, given the high deployment overhead of modern sensor networks. Here we offer an in-depth exploration of state-of-polarization sensing over fiber-optic networks using unmodified optical transceivers to establish a strong correlation with ground truth distributed acoustic sensing. To validate our sensing methodology, we collect 85 days of polarization and distributed acoustic sensing measurements along two colocated, 50 km fiber-optic cables in Southern California. We then examine how polarization sensing can improve network reliability by accurately modeling overall network health and preemptively detecting traffic loss. Finally, we explore the feasibility of wide-scale seismic monitoring with polarization sensing, showcasing the polarization perturbations following low-intensity earthquakes and the potential to more than double seismic monitoring coverage in Southern California alone.

Abstract The spread of invasive species often follows a jump-dispersal pattern. While jumps are typically fostered by humans, local dispersal can occur due to the specific traits of a species, which are often poorly understood. This holds true for small hive beetles (Aethina tumida), which are parasites of social bee colonies native to sub-Saharan Africa. They have become a widespread invasive species. In 2017, a mark-release-recapture experiment was conducted in six replicates (A–F) using laboratory reared, dye-fed adults (N = 15,690). Honey bee colonies were used to attract flying small hive beetles at fixed spatial intervals from a central release point. Small hive beetles were recaptured (N = 770) at a maximum distance of 3.2 km after 24 h and 12 km after 1 week. Most small hive beetles were collected closest to the release point at 0 m (76%, replicate A) and 50 m (52%, replicates B to F). Temperature and wind deviation had significant effects on dispersal, with more small hive beetles being recaptured when temperatures were high (GLMM: slope = 0.99, SE = 0.17, Z = 5.72, P

Abstract The mid-Piacenzian warm period (MPWP, ~3.264–3.025 Ma) has gained widespread interest due to its partial analogy with future climate. However, quantitative data–model comparison of East Asian Summer Monsoon (EASM) precipitation during the MPWP is relatively rare, especially due to problems in decoding the imprint of physical processes to climate signals in the records. In this study, pollen-based precipitation records are reconstructed and compared to the multi-model ensemble mean of the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2). We find spatially consistent precipitation increase in most simulations but a spatially divergent change in MPWP records. We reconcile proxy data and simulation by decomposing physical processes that control precipitation. Our results 1) reveal thermodynamic control of an overall enhancement of EASM precipitation and 2) highlight a distinct control of thermodynamic and dynamical processes on increases of tropical and subtropical EASM precipitation, reflecting the two pathways of water vapor supply that enhance EASM precipitation, respectively.

Abstract Cochlear implant users experience difficulties controlling their vocalizations compared to normal hearing peers. However, less is known about their voice quality. The primary aim of the present study was to determine if cochlear implant users’ voice quality would be categorized as dysphonic by the Acoustic Voice Quality Index (AVQI) and smoothed cepstral peak prominence (CPPS). A secondary aim was to determine if vocal quality is further impacted when using bilateral implants compared to using only one implant. The final aim was to determine how residual hearing impacts voice quality. Twenty-seven cochlear implant users participated in the present study and were recorded while sustaining a vowel and while reading a standardized passage. These recordings were analyzed to calculate the AVQI and CPPS. The results indicate that CI users’ voice quality was detrimentally affected by using their CI, raising to the level of a dysphonic voice. Specifically, when using their CI, mean AVQI scores were 4.0 and mean CPPS values were 11.4 dB, which indicates dysphonia. There were no significant differences in voice quality when comparing participants with bilateral implants to those with one implant. Finally, for participants with residual hearing, as hearing thresholds worsened, the likelihood of a dysphonic voice decreased.

Introduction Snakebite envenoming (SBE) results in over 500 000 deaths or disabling injuries annually. Varespladib methyl, an oral inhibitor of secretory phospholipase A2, is a nearly ubiquitous component of snake venoms. We conducted a phase II clinical trial to assess efficacy and safety of oral varespladib methyl in patients bitten by venomous snakes.Methods This double-blind, randomised, placebo-controlled trial enrolled patients in emergency departments in India and the USA. Patients with SBE were randomly assigned (1:1) to receive varespladib methyl or placebo two times per day for 1 week. All patients received standard of care, including antivenom. The primary outcome was change in the composite Snakebite Severity Score (SSS) measuring the severity of envenoming, from baseline to the average composite SSS at 6 and 9 hours.Results Among 95 patients randomised August 2021 through November 2022, the most common snakebites were from Russell’s vipers (n=29), copperheads (n=18) and rattlesnakes (n=14). The SSS improved from baseline to the average at 6 and 9 hours by 1.1 (95% CI, 0.7 to 1.6) in the varespladib group versus 1.5 (95% CI, 1.0 to 2.0) in the placebo group (difference −0.4, 95% CI, −0.8 to 0.1, p=0.13). While key secondary outcomes were not statistically different by treatment group, benefit was seen in the prespecified subgroup initiating study drug within 5 hours of bite (n=37). For this early treatment group, clinically important differences were observed for illness severity over the first week, patient-reported function on days 3 and 7 and complete recovery. No death or treatment emergent serious adverse event occurred.Conclusion For emergency department treatment of snakebites, the addition of varespladib to antivenom did not find evidence of difference for the primary outcome based on the SSS. A potentially promising signal of benefit was observed in patients initiating treatment within 5 hours of snakebite.

In this study, we develop new reverse engineering (RE) techniques to identify the organization of the synaptic inputs generating firing patterns of populations of neurons. We tested these techniques in silico to allow rigorous evaluation of their effectiveness, using remarkably extensive parameter searches enabled by massively-parallel computation on supercomputers. We chose spinal motoneurons as our target neural system, since motoneurons process all motor commands and have well-established input-output properties. One set of simulated motoneurons was driven by 300,000+ simulated combinations of excitatory, inhibitory, and neuromodulatory inputs. Our goal was to determine if these firing patterns had sufficient information to allow RE identification of the input combinations. Like other neural systems, the motoneuron input-output system is likely non-unique. This non-uniqueness could potentially limit this RE approach, as many input combinations can produce similar outputs. However, our simulations revealed that firing patterns contained sufficient information to sharply restrict the solution space. Thus, our RE approach successfully generated estimates of the actual simulated patterns of excitation, inhibition, and neuromodulation, with variances accounted for ranging from 75–90%. It was striking that nonlinearities induced in firing patterns by the neuromodulation inputs did not impede RE, but instead generated distinctive features in firing patterns that aided RE. These simulations demonstrate the potential of this form of RE analysis. It is likely that the ever-increasing capacity of supercomputers will allow increasingly accurate RE of neuron inputs from their firing patterns from many neural systems.

Galectin-9 (Gal-9) is a tandem-repeat galectin with diverse roles in immune homeostasis, inflammation, malignancy, and autoimmune diseases. In cancer, Gal-9 displays variable expression patterns across different tumor types. Its interactions with multiple binding partners, both intracellularly and extracellularly, influence key cellular processes, including immune cell modulation and tumor microenvironment dynamics. Notably, Gal-9 binding to cell-specific glycoconjugate ligands has been implicated in both promoting and suppressing tumor progression. Here, we provide insights into Gal-9 and its involvement in immune homeostasis and cancer biology with an emphasis on multiple myeloma (MM) pathophysiology, highlighting its complex and context-dependent dual functions as a pro- and anti-tumorigenic molecule and its potential implications for therapy in MM patients.

Introduction: Endoscopic ultrasound (EUS)-guided lumen-apposing metal stents (LAMS) represent a novel tool in therapeutic endoscopy. However, the presence of LAMS may dissuade surgeons from operations with curative-intent. We report three clinical scenarios with deployment of LAMS in patients that subsequently underwent pancreaticoduodenectomy (PD). Methods: Six patients identified from our IRB-approved pancreas cancer database had EUS-LAMS placement prior to PD. Patient, tumor, treatment-related variables, and outcomes are herein reported. Results: Two patients underwent a LAMS gastrojejunostomy (GJ) for duodenal obstruction. Another patient underwent LAMS choledochoduodenostomy (CDS) for malignant biliary obstruction. In three patients, a LAMS gastrogastrostomy or jejunogastrostomy was deployed post Roux-en-Y gastric bypass (RYGB) for a EUS-directed transgastric ERCP (EDGE) procedure. The hospital length of stay after LAMS placement was 0–3 days without morbidity. Patients subsequently proceeded to either classic PD (n = 5) or PPPD (n = 1). Interval from LAMS insertion to surgery ranged from 28 to 194 days. Mean PD operative time and EBL were 513 minutes and 560 mL, respectively. Post-PD hospital length of stay was 4–17 days. Clavien-Dindo IIIb morbidity required percutaneous drainage of intra-abdominal collections in two patients. In cases involving LAMS-GJ and CDS, the LAMS directly impacted the surgeon's preference not to perform pylorus preservation. Conclusions: In this case series, PD following EUS-LAMS was feasible with acceptable morbidity. Additional studies with larger patient populations are needed to evaluate LAMS as a bridge to PD with curative-intent.

Abstract Background Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9–13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC. Methods Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40–50 Gy in 4–5 fractions with target and OAR delineation per institutional standards. Endpoints included local control per RECIST v1.1, distant failure, overall survival (OS), and acute and chronic toxicities per Common Terminology Criteria for Adverse Events, v5. Results Fifteen patients with LR-PAC were identified with median follow-up of 10.6 mos (2.8–26.5 mos) from MRgSBRT. There were 8 females and 7 males, with a median age of 69 years (50–83). One patient underwent neoadjuvant radiation for 50.4 Gy in 28 fractions followed by resection, and one underwent adjuvant radiation for 45 Gy in 25 fractions prior to recurrence. MRgSBRT was delivered a median of 18.8 mos (3.5–52.8 mos) following resection. OS following recurrence at 6 and 12 mos were 87% and 51%, respectively, with a median survival time of 14.1 mos (3.2–27.4 mos). Three patients experienced local failure at 5.9, 7.8, and 16.6 months from MgSBRT with local control of 92.3% and 83.9% at 6 and 12 months. 10 patients experienced distant failure at a median of 2.9 mos (0.3–6.7 mos). Grade 1–2 acute GI toxicity was noted in 47% of patients, and chronic GI toxicity in 31% of patients. No grade > 3 toxicities were noted. Conclusions This is the first report on toxicity and outcomes of MRgSBRT for LR-PAC in the literature. MRgSBRT is a safe, feasible treatment modality with the potential for improved local control in this vulnerable population. Future research is necessary to better identify which patients yield the most benefit from MRgSBRT, which should continue to be used with systemic therapy as tolerated. Trial Registration: Jefferson IRB#20976, approved 2/17/21.

Abstract In 2017, a novel influenza A virus (IAV) was isolated from an Egyptian fruit bat. In contrast to other bat influenza viruses, the virus was related to avian A(H9N2) viruses and was probably the result of a bird-to-bat transmission event. To determine the cross-species spill-over potential, we biologically characterize features of A/bat/Egypt/381OP/2017(H9N2). The virus has a pH inactivation profile and neuraminidase activity similar to those of human-adapted IAVs. Despite the virus having an avian virus–like preference for α2,3 sialic acid receptors, it is unable to replicate in male mallard ducks; however, it readily infects ex-vivo human respiratory cell cultures and replicates in the lungs of female mice. A/bat/Egypt/381OP/2017 replicates in the upper respiratory tract of experimentally-infected male ferrets featuring direct-contact and airborne transmission. These data suggest that the bat A(H9N2) virus has features associated with increased risk to humans without a shift to a preference for α2,6 sialic acid receptors.

Abstract Optimal therapeutic and diagnostic efficacy is essential for healthcare's global mission of advancing oncologic drug development. Accurate diagnosis and detection are crucial prerequisites for effective risk stratification and personalized patient care in clinical oncology. A paradigm shift is emerging with the promise of multi‐receptor‐targeting compounds. While existing detection and staging methods have demonstrated some success, the traditional approach of monotherapy is being reevaluated to enhance therapeutic effectiveness. Heterodimeric site‐specific agents are a versatile solution by targeting two distinct biomarkers with a single theranostic agent. This review describes the innovation of dual‐targeting compounds, examining their design strategies, therapeutic implications, and the promising path they present for addressing complex diseases.

Introduction: Pancytopenia in the peripheral smear and hypocellularity in the bone marrow characterise aplastic anaemia (AA). It is far less common in Western countries. The Asian continent has a greater prevalence rate. Aplastic anemia carries a high mortality rate if it is not treated. Hence early diagnosis and treatment is important to reduce the mortality rate. Only few Indian studies are conducted to assess the epidemiology of AA. Aims and Objectives: To evaluate clinical and pathological profile of patients with aplastic anemia. Materials and Methods: This cross sectional observational study was done over a period of 1.5years in department of medicine, St johns medical college, Bangalore. A detailed clinical history, physical examination and available previous investigations were recorded. Results: In our study aplastic anemia had bimodal peak in age distribution noted in groups of 21-30 & 51-60yrs .Male preponderance of 1.33:1 .Most common presenting complaint was Fatigue. Severe (37.6%) and Very severe aplastic anemia (37.6%) were more common.Most common 1st line agent was Cyclosporine and 2nd line agent was Danazol. Out the 35 only 4 (11.4%) showed Complete Response, 19 (54.3%) showed Partial Remission, 10 were transfusion dependent (28.6%) and 2 (5.8%) expired. Conclusion: ATG and Cyclosporine showed significant improvement in most parameters. Many patients in the study were unwilling for ATG and bone marrow transplantation due to the cost factor. Many are still requiring frequent transfusions, thus probing us to search for newer novel forms of treatment to reduce the cost of treatment and mortality in aplastic anemia patients.

Objective: To develop a deep learning algorithm for the analysis of patch testing. Patients and Methods: A retrospective case series between January 1, 2010, and December 31, 2020, was constructed to develop a deep learning model for the classification of patch test results from photographs. The performance of human expert readers reviewing the same photographs blinded to the original clinical physical examination findings was measured to benchmark model performance. Results: Model performance on the independent test set (n=5070 test site locations from 37 patients) achieved an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.86-0.91) and an F1 score of 37.1. The optimal cutoff had a sensitivity of 70.1% (136/194; 95% CI, 63.1%-76.5%) and a specificity of 91.7% (4472/4876; 95% CI, 90.9%-92.5%). Conclusion: We demonstrated proof-of-concept utility for detecting allergic contact dermatitis using an automated deep learning approach.

Summary: The maintenance of homeostasis and rapid regeneration of the urothelium following stress are critical for bladder function. Here, we identify a key role for IFRD1 in maintaining urothelial homeostasis in a mouse model. We demonstrate that the murine bladder expresses IFRD1 at homeostasis, particularly in the urothelium, and its loss alters the global transcriptome with significant accumulation of endolysosomes and dysregulated uroplakin expression pattern. We show that IFRD1 interacts with mRNA-translation-regulating factors in human urothelial cells. Loss of Ifrd1 leads to disrupted proteostasis, enhanced endoplasmic reticulum (ER stress) with activation of the PERK arm of the unfolded protein response pathway, and increased oxidative stress. Ifrd1-deficient bladders exhibit urothelial cell apoptosis/exfoliation, enhanced basal cell proliferation, reduced differentiation into superficial cells, increased urothelial permeability, and aberrant voiding behavior. These findings highlight a crucial role for IFRD1 in urothelial homeostasis, suggesting its potential as a therapeutic target for bladder dysfunction.

Identifying novel risk-resilient diets is urgent to address food insecurity and tackle global hunger and malnutrition. This study evaluated the suitability of mesquite (Neltuma spp.) pod flours as food staples for human nourishment and compared nutritional properties of mesquites growing natively or as introduced species in the drylands of Mexico, Kenya and Tanzania. Using gas chromatography and mass spectrometry, we analysed chemical composition, dietary fibre, antinutrients, amino acids and fatty acids of pod flours from Neltuma laevigata, N. laevigata × N. odorata and N. velutina (abundant native species of Northern Mexico). We also studied the introduced N. juliflora from Kenya, and N. pallida from Tanzania which have become invasive. This research demonstrates that mesquite flour contains all the essential amino acids, with the highest being valine, leucine and lysine. The most abundant non-essential amino acids are aspartate, glutamate and proline. Mesquite flours are rich in palmitic, oleic and linolenic acids. Besides this, mesquite flour is abundant in phenols and contains less gallic and phytic acids than wheat. We show that nutritionally, mesquite flours are comparable to wheat flour. These findings demonstrate that Neltuma pod flours are excellent candidates to reduce malnutrition and hunger for the poorest people of the world.

Background: An external vendor providing off-the-shelf spinal orthoses to inpatients created significant costs and barriers to quality care for spinal surgery patients. A nursing leadership team initiated a quality improvement project to reduce the cost of providing off-the-shelf spinal orthoses and improve the care provided to spinal patients. Objective: To develop and evaluate a nursing-led process for providing off-the-shelf orthoses to spinal surgery patients and eliminate high costs. Design: Quality improvement project evaluated as a retrospective interrupted time-series Setting: Post Surgery Inpatient Unit Level II Trauma Center in a United States hospital located in Florida Participants: Vendor Program: 134 patients; Centralized Program: 155 patients Methods: The nursing leadership team developed a centralized spinal orthoses program where the bedside nurse fitted the patient with a spinal orthosis, eliminating the need for an external orthotist. The study quantifies changes in study metrics by comparing patients identified through chart review who received care in the vendor program to those who received care in the centralized program utilizing nonparametric statistical techniques. Results: The centralized nursing-led spinal orthosis program allowed the unit to mobilize patients more quickly than patients managed under the vendor program (3.85 hr. [95 % CI: 1.27 to 7.26 hrs] reduction; p = 0.004). The overall length of stay was reduced by 0.78 days ([1.34 – 0.02 days]; p = 0.063) or 18.72 h. While the statistical test did not indicate significance, the 18.72-hour reduction in length of stay represents a potential clinically relevant finding. Evaluating patients that suffered a primary spinal injury and no complications (vendor program: 54 patients; centralized program: 86 patients) showed a similar reduction in time to mobilization (4.5 hr reduction [0.53 to 12.93 hrs]; p = 0.025), but the length of stay reduction increased to 1.02 days [0.12 to 1.97 days], a difference determined to be statistically significant (p = 0.014). Centralizing the process for providing off-the-shelf spinal orthoses reduced the cost of a thoracic-lumbar sacral orthosis by $1,483 and the price of a lumbar-sacral orthosis by $1,327. Throughout the study, the new program reduced the cost of providing spinal orthoses by $175,319. Conclusions: The results demonstrate that the nursing-led centralized spinal orthosis program positively impacted the quality of care provided to our patients while also reducing the cost of delivering the orthoses. Tweetable abstract: A nursing-led centralized spinal orthosis program reduces the cost of care while reducing time to mobilization and length of stay.

The western portion of the Pacific Northwest is known for being dry in the summer and cool and humid in the other months. Tall fescue is valued for its drought and heat tolerance, making it a desirable choice in regions where water is scarce and often restricted by legislation during periods of drought in the summer. However, cool and humid climates make it challenging to manage tall fescue in the winter because unacceptable quality is often observed due to low-temperature diseases and thinning in turf. A field trial was initiated in Autumn 2020 in Corvallis, OR, USA to assess the effects of mowing height as well as fertility timing and rate on tall fescue performance. Two mowing heights of 5.1 and 7.6 cm, four seasonal fertility timings, and three levels of annual N rates of 98, 196, and 294 kg·ha−1·yr−1 were evaluated using a 2 × 4 × 3 factorial experiment in a strip-plot design. Quantitative data of percent green cover and normalized difference vegetation index (NDVI) suggest that autumn fertilization is needed in cool, humid areas where tall fescue is actively growing in the winter months. The annual fertilization rate of 294 kg·ha−1·yr−1 N produced higher green turf cover and NDVI, compared with 98 or 196 kg·ha−1·yr−1 N. Furthermore, divergent effects of mowing heights were observed during winter compared with other months, suggesting that tall fescue could be mowed lower at 5.1 cm during cool, humid winter months and higher at 7.6 cm in other seasons for better overall turfgrass growth and less winter disease and thinning. Our research provides practical cultural practices for managing tall fescue turf in the Pacific Northwest or similar climates.

Parasites are important component of communities in a forest ecosystem with profound effects on trophic interactions such as food web. Modification of the forest structure (e.g. changes in species composition and abundance of key species) can have a strong impact on the occurrence, diversity, and abundance of parasites, with subsequent repercussions for ecosystem functioning. In this study, we compared the occurrence and abundance of wild rodents’ ectoparasites from forest sites invaded and uninvaded by an invasive tree, Maesopsis eminii in Amani Nature Forest Reserve, Tanzania. Three large plots (40 m × 100 m) were randomly established in each forest sites invaded and uninvaded by M. eminii. In each plot, 50 Sherman traps were systematically placed at 10 m interval for capturing wild rodents through a capture-mark-recapture technique. Wilcox rank sum test was used to compare for differences in the abundance of infested rodents and ectoparasites between the invaded and uninvaded forest sites. A total of 297 individual rodents were captured and screened for ectoparasites, including 174 rodents from uninvaded forest site and 123 rodents from invaded forest site. The number of infested rodents were significantly (W = 8592, P

Animals exhibit dynamic movement and activity in response to environmental variation including changes in reproductive opportunities, predation risk, or food availability. Yet, it remains unclear which factors are primary in affecting animal movement, and whether the relative importance of these factors are consistent through time. We tracked snowshoe hares (Lepus americanus) using GPS telemetry during eight summers spanning a hare population cycle (2015–2022) in southwestern Yukon, Canada, to determine associations between environmental variation and hare movement and home range size. Hare density varied 25-fold during the study and home range size increased markedly during low hare density, especially for males. Both sexes retained similar core space use and linearity of movements, but at low densities males had greater and more variable movement rates and time spent travelling. Trail cameras revealed that annual changes in hare movement were also correlated with relative abundance of lynx (Lynx canadensis) and coyotes (Canis latrans). However, hare detection rates within a season were not closely associated with seasonal variation in predator detection. Observed differences between male and female hares in some metrics highlighted that different life histories and reproductive behavior are likely the main drivers of hare movement dynamics. Therefore, fitness rewards associated with successful mate search and reproduction appear to outweigh risks associated with increased movement, even in highly variable environments where costs of prioritizing reproduction-related activities are notably high and variable.

# Background Pelvic floor dysfunction (PFD) occurs when muscles of the pelvic floor become weakened, impaired, or experience tension leading to a variety of complications. Due to the reactive nature and high demands of many sports, athletes are at increased susceptibility and of particular interest concerning PFD. # Hypothesis/Purpose The purpose of this study was to explore the prevalence of PFD among college-aged athletes, assess how PFD impacted athletic performance, and identify contributing factors for increased likelihood of PFD in athletes. # Study Design Cross-Sectional Study # Methods All fully active LVC NCAA Division 3 athletes were recruited for screening for PFD using the Cozean Pelvic Dysfunction Screening Protocol and were surveyed on their self-knowledge of PFD. Athletes who scored ≥ 3 on this tool completed an additional survey, created by the investigators, to identify the impact PFD had on their athletic performance and personal life and were then randomly assigned to one of three investigators to undergo a noninvasive coccygeal assessment to determine underactive, overactive, or normal pelvic floor muscle (PFM) activity. # Results Fifty-three Division III male and female athletes between the ages of 18-25 years old participated in the study. Statistically significant differences were found between Cozean scores and demographic factors of age (*p* \

Objective: Carotid endarterectomy (CEA) is the gold standard for revascularization of atherosclerotic extra-cranial carotid artery lesions. The introduction of transfemoral carotid artery stenting (TFCAS) led to multiple randomized controlled trials to compare the safety and efficacy of an endovascular approach against traditional CEA in the management of carotid artery stenosis. The operative management of carotid artery stenosis continues to evolve, with the more recent introduction of TransCarotid artery revascularization (TCAR) and a novel flow-reversal neuroprotection system. This manuscript reviews a brief history regarding carotid artery revascularization, as well as the indications, technical considerations, and clinical outcomes of the TCAR procedure. Technical considerations: The preoperative, intraoperative, and postoperative medical and technical considerations are explored. Topics of discussion will include the indications and contraindications for TCAR, anatomic requirements, instructions for use (IFU) and off-label utility, optimal pharmacologic regimen with carotid stent placement, standard deployment and suggestions for hostile anatomy, as well as recommended postoperative management and surveillance imaging. Discussion: The Society for Vascular Surgery (SVS) has published a consensus statement on the pathways available to obtain clinical competency and maintain technical proficiency with TCAR. Meta-analyses reviewing the contemporary technical success and clinical outcomes of TCAR have demonstrated high rates of procedural success and low rates of stroke, myocardial infarction, and death. Studies have further illustrated comparable one-year rates of peri‑procedural stroke between TCAR and CEA, for asymptomatic and symptomatic carotid lesions, with both outperforming TFCAS. Conclusion: Management of extra-cranial carotid artery stenosis utilizing TCAR with the ENROUTE flow-reversal neuroprotection system has been widely adopted, yielding clinical outcomes and stroke prevention similar to traditional CEA and superior to TFCAS.

Abstract Herein, a robust microporous aluminum tetracarboxylate framework, MIL‐120(Al)‐AP, (MIL, AP: Institute Lavoisier and Ambient Pressure synthesis, respectively) is reported, which exhibits high CO2 uptake (1.9 mmol g−1 at 0.1 bar, 298 K). In situ Synchrotron X‐ray diffraction measurements together with Monte Carlo simulations reveal that this structure offers a favorable CO2 capture configuration with the pores being decorated with a high density of µ2‐OH groups and accessible aromatic rings. Meanwhile, based on calculations and experimental evidence, moderate host‐guest interactions Qst (CO2) value of MIL‐120(Al)‐AP (−40 kJ mol−1) is deduced, suggesting a relatively low energy penalty for full regeneration. Moreover, an environmentally friendly ambient pressure green route, relying on inexpensive raw materials, is developed to prepare MIL‐120(Al)‐AP at the kilogram scale with a high yield while the Metal‐ Organic Framework (MOF) is further shaped with inorganic binders as millimeter‐sized mechanically stable beads. First evidences of its efficient CO2/N2 separation ability are validated by breakthrough experiments while operando IR experiments indicate a kinetically favorable CO2 adsorption over water. Finally, a techno‐economic analysis gives an estimated production cost of ≈ 13 $ kg−1, significantly lower than for other benchmark MOFs. These advancements make MIL‐120(Al)‐AP an excellent candidate as an adsorbent for industrial‐scale CO2 capture processes.

Summary: Phosphate (Pi) serves countless metabolic pathways and is involved in macromolecule synthesis, energy storage, cellular signaling, and bone maintenance. Herein, we describe the coordination of Pi uptake and efflux pathways to maintain mammalian cell Pi homeostasis. We discover that XPR1, the presumed Pi efflux transporter, separately supervises rates of Pi uptake. This direct, regulatory interplay arises from XPR1 being a binding partner for the Pi uptake transporter PiT1, involving a predicted transmembrane helix/extramembrane loop in XPR1, and its hitherto unknown localization in a subset of intracellular LAMP1-positive puncta (named “XLPVs”). A pharmacological mimic of Pi homeostatic challenge is sensed by the inositol pyrophosphate IP8, which functionalizes XPR1 to respond in a temporally hierarchal manner, initially adjusting the rate of Pi efflux, followed subsequently by independent modulation of PiT1 turnover to reset the rate of Pi uptake. These observations generate a unifying model of mammalian cellular Pi homeostasis, expanding opportunities for therapeutic intervention.

Background and Aims: Drug-induced liver injury (DILI) is a major failure mode in pharmaceutical development. This study aims to address the limitations of existing preclinical models by assessing a high-throughput, microfluidic liver-on-a-chip system, termed “Curio Barrier Liver Chips,” and its capacity to recapitulate the effects of chronic hepatotoxic drug treatment through metabolic and phenotypic characterization. Methods: Curio Barrier liver chips (Curiochips), fabricated in an 8 × 2 well configuration, were utilized to establish three dimensional liver organoid cultures. Human-induced pluripotent stem cells were differentiated into human liver organoids, and their viability, liver-specific functions, and pharmacological responses were assessed over 28 days. Results: The Curiochips successfully maintained liver physiology and function, showing strong albumin secretion and cytochrome (CYP) P450 activities for 28 days. Unlike traditional models requiring millimolar drug concentrations to detect hepatotoxicity, this platform showed increased sensitivity for acetaminophen and fialuridine at micromolar concentrations. In situ differentiation of foregut spheroids to liver organoids was also achieved, further simplifying the establishment of liver chips. Furthermore, the chips demonstrated viability, function, and DILI responsiveness for 28 days, making this an improved model for studying idiosyncratic DILI with prolonged drug exposure and high-throughput capabilities compared to other available systems or primary human hepatocytes. Conclusion: The Curiochips offer an advanced, miniaturized in vitro model for early-stage drug development and a sensitive, responsive, and cost-effective means to detect direct hepatotoxicity. Induced pluripotent stem cell liver organoids, in conjunction with the Curiochip, deliver a high-throughput platform with robust functionality and pharmacological responsiveness that make it a promising tool for improving the prediction and understanding of DILI risk prediction, especially with prolonged drug exposure. The model also opens new avenues for research in other chronic liver diseases.

Abstract Background No single marker of bladder cancer (BC) exists in urine samples with sufficient accuracy for disease diagnosis and treatment monitoring. The multiplex Oncuria BC assay noninvasively quantifies the concentration of 10 protein analytes in voided urine samples to quickly generate a unique molecular profile with proven BC diagnostic and treatment-tracking utility. Test adoption by diagnostic and research laboratories mandates reliably reproducible assay performance across a variety of instrumentation platforms used in different laboratories. Methods We compared the performance of the clinically validated Oncuria BC multiplex immunoassay when data output was generated on three different analyzer systems. Voided urine samples from 36 subjects (18 with BC and 18 Controls) were reacted with Oncuria test reagents in three 96-well microtiter plates on Day 1, and consecutively evaluated on the LED/image-based MagPix, and laser/flow-based Luminex 200 and FlexMap 3D (all xMAP instruments from Luminex Corp., Austin, TX) on Day 2. The BC assay uses magnetic bead-based fluorescence technology (xMAP, Multi-analyte profiling; Luminex) to simultaneously quantify 10 protein analytes in urine specimens [i.e., angiogenin (ANG), apolipoprotein E (ApoE), carbonic anhydrase IX (CA9), CXCL8/interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-10 (MMP-10), serpin A1/alpha-1 anti-trypsin (A1AT), serpin E1/plasminogen activator inhibitor-1 (PAI-1), CD138/syndecan-1 (SDC1), and vascular endothelial growth factor-A (VEGF-A)]. All three analyzers quantify fluorescence signals generated by the Oncuria assay. Results All three platforms categorized all 10 analytes in identical samples at nearly identical concentrations, with variance across systems typically

Abstract Animals are exposed to many microbes in their environment, some of which have been shown to colonize various tissues including the intestine. The composition of the intestinal microbiota affects many aspects of the host’s physiology and health. Despite this, very little is known about whether host behavior contributes to the colonization. We approach this question in the nematode C. elegans, which feeds on bacteria and also harbors an intestinal microbiome. We examined the behavior of C. elegans towards CeMbio, a simplified microbiome consisting of twelve strains that represent the bacteria found in the animal’s natural environment. We observed that C. elegans raised on E. coli shows a strong preference for three members of CeMbio (Lelliottia amnigena JUb66, Enterobacter hormaechei CEent1, and Pantoea nemavictus BIGb0393) compared to E. coli. Previously, these three bacterial strains have been shown to support faster C. elegans development time than E. coli OP50 and are low colonizers compared to eight other members of CeMbio. We then used gas chromatography coupled to mass spectrometry to identify that these three bacteria release isoamyl alcohol, a previously described C. elegans chemoattractant. We suggest that C. elegans seeks bacteria that release isoamyl alcohol and support faster growth.

Abstract Background Hidden Markov Models (HMMs) are often used to model multi-state capture-recapture data in ecology. However, a variety of HMM modeling approaches and software exist, including both maximum likelihood and Bayesian methods. The diversity of these methods obscures the underlying HMM and can exaggerate minor differences in parameterization. Methods In this paper, we describe a general framework for modelling multi-state capture-recapture data via HMMs using both maximum likelihood and Bayesian methods. We then apply an HMM to invasive silver carp telemetry data from the Illinois River and compare the results estimated by both methods. Results Our analysis demonstrates disadvantages of relying on a single approach and highlights insights obtained from implementing both methods together. While both methods often struggled to converge, our results show biologically informative priors for Bayesian methods and initial values for maximum likelihood methods can guide convergence toward realistic solutions. Incorporating prior knowledge of the system can successfully constrain estimation to biologically realistic movement and detection probabilities when dealing with sparse data. Conclusions Biologically unrealistic estimates may be a sign of poor model convergence. In contrast, consistent convergence behavior across approaches can increase the credibility of a model. Estimates of movement probabilities can strongly influence the predicted population dynamics of a system. Therefore, thoroughly assessing results from HMMs is important when evaluating potential management strategies, particularly for invasive species.

Objective: Acupuncture is an effective treatment for arrythmias and postoperative symptoms but has not been investigated after cardiac surgery. Acupuncture After Heart Surgery is a prospective, randomized, controlled pilot trial of daily inpatient acupuncture or standard care after valve surgery with the primary end point being feasibility and secondary end points being reduction in postoperative atrial fibrillation incidence and postoperative symptoms. Methods: A total of 100 patients without a history of atrial fibrillation underwent primary valve surgery via sternotomy and randomized 1:1 to acupuncture (51) or standard care (49). The acupuncture group received daily inpatient sessions starting on postoperative day 1. Postoperative symptoms (pain, nausea, stress, anxiety) were assessed once daily in the standard care group and before/after daily intervention in the acupuncture group. The groups were comparable except for age (acupuncture: 55.6 ± 11.4 years, standard care: 61.0 ± 9.3 years; P = .01). Results: The Acupuncture After Heart Surgery pilot trial met primary and secondary end points. There were no adverse events. An average of 3.8 (±1.1) acupuncture sessions were delivered per patient during a mean hospital stay of 4.6 days (±1.3). Acupuncture was associated with a reduction in pain, nausea, stress, and anxiety after each session (P

Abstract Mustn1, a gene expressed exclusively in the musculoskeletal system, was shown in previous in vitro studies to be a key regulator of myogenic differentiation and myofusion. Other studies also showed Mustn1 expression associated with skeletal muscle development and hypertrophy. However, its specific role in skeletal muscle function remains unclear. This study sought to investigate the effects of Mustn1 in a conditional knockout (KO) mouse model in Pax7 positive skeletal muscle satellite cells. Specifically, we investigated the potential effects of Mustn1 on myogenic gene expression, grip strength, alterations in gait, ex vivo investigations of isolated skeletal muscle isometric contractions, and potential changes in the composition of muscle fiber types. Results indicate that Mustn1 KO mice did not present any substantial phenotypic changes or significant variations in genes related to myogenic differentiation and fusion. However, an approximately 10% decrease in overall grip strength was observed in the 2‐month‐old KO mice in comparison to the control wild type (WT), but this decrease was not significant when normalized by weight. KO mice also generated approximately 8% higher vertical force than WT at 4 months in the hindlimb. Ex vivo experiments revealed decreases in about 20 to 50% in skeletal muscle contractions and about 10%–20% fatigue in soleus of both 2‐ and 4‐month‐old KO mice, respectively. Lastly, immunofluorescent analyses showed a persistent increase of Type IIb fibers up to 15‐fold in the KO mice while Type I fibers decreased about 20% and 30% at both 2 and 4 months, respectively. These findings suggest a potential adaptive or compensatory mechanism following Mustn1 loss, as well as hinting at an association between Mustn1 and muscle fiber typing. Collectively, Mustn1's complex roles in skeletal muscle physiology requires further research, particularly in terms of understanding the potential role of Mustn1 in muscle repair and regeneration, as well as with influence of exercise. Collectively, these will offer valuable insights into Mustn1's key biological functions and regulatory pathways.

Pecan (Carya illinoensis), an economically important deciduous tree, bears commercially valuable nutritional nuts. Spring freezes in April can severely injure pecan buds, decreasing bloom, and fruit set. This study determined how low temperatures affect pecan buds/flowers at different growth stages in several pecan scion/rootstock combinations. This study focused on three pecan scion/rootstock combinations: Pawnee/Peruque (PP), Kanza/Giles (KG), and Maramec/Colby (MC), grown at the Cimarron Valley Research Station, Perkins, Oklahoma. Branches at three different growth stages, i.e., outer bud scale shed, one week after bud break, and early bloom stages were collected from PP, MC, and KG. Branches were held in a Conviron E8 freezing unit at 4 temperatures (-2, 0, 2, and 4°C) for 4 and 8 hours; A total of 8 treatments. One sample set was kept as an untreated control. After 2–3 weeks, branch samples from all the temperature treatments were observed and categorized into two groups. Group one with number of branches had healthy buds/formation of healthy leaves/flowers and group two with number of dead branches. The carbohydrate content reserved from dormant was analyzed using an Anthrone reagent. Visual observations and carbohydrate analyses revealed differences in damage and carbohydrate content among the scion/rootstock combinations, low-temperature treatments, and growth stages. The MC combination had minimum visual damage to leaves, buds, and flowers and significantly lower soluble sugars and starch in bark phloem as well as significantly lower soluble sugars in woody tissue xylem. The KG combination had maximum visual damage and significantly higher soluble sugars and starches in the bark, and soluble sugars in the woody tissues. These results indicate the MC combination is more tolerant to spring freeze damage at all three growth stages compared to the other two pecan scion/rootstock combinations. The results also demonstrate the MC combination is using more non-structural carbohydrates, soluble sugars and starches, suggesting this is a possible mechanism in its freeze tolerance.

Vascular cell adhesion is a complex orchestration of events that commonly feature lectin–ligand interactions between circulating cells, such as immune, stem, and tumor cells, and endothelial cells (ECs) lining post-capillary venules. Characteristically, circulating cell adherence to the vasculature endothelium is initiated through interactions between surface sialo-fucosylated glycoprotein ligands and lectins, specifically platelet (P)- or endothelial (E)-selectin on ECs or between leukocyte (L)-selectin on circulating leukocytes and L-selectin ligands on ECs, culminating in circulating cell extravasation. This lectin–ligand interplay enables the migration of immune cells into specific tissue sites to help maintain effective immunosurveillance and inflammation control, the homing of stem cells to bone marrow or tissues in need of repair, and, unfortunately, in some cases, the dissemination of circulating tumor cells (CTCs) to distant metastatic sites. Interestingly, there is a growing body of evidence showing that the family of β-galactoside-binding lectins, known as galectins, can also play pivotal roles in the adhesion of circulating cells to the vascular endothelium. In this review, we present contemporary knowledge on the significant roles of host- and/or tumor-derived galectin (Gal)-3, -8, and -9 in facilitating the adhesion of circulating cells to the vascular endothelium either directly by acting as bridging molecules or indirectly by triggering signaling pathways to express adhesion molecules on ECs. We also explore strategies for interfering with galectin-mediated adhesion to attenuate inflammation or hinder the metastatic seeding of CTCs, which are often rich in galectins and/or their glycan ligands.

Students with Learning Disabilities (LDs) can experience classroom challenges that may negatively impact their social and emotional development, and these struggles can put them at risk for mental health issues and lower quality of life. Programs designed to support students with LDs need to consider not only academic skills and accommodations, but also the broader well-being of these students. Among interventions that address holistic student development are mentoring programs that utilize peer mentors (older students who also have LDs). The purpose of this article was to review key literature on the potential benefits of peer mentoring for students with LDs. According to reviewed articles, peer mentoring programs have been implemented in both school and university settings. In addition to conferring academic benefits to mentees, participation in these programs is associated with increased emotional well-being, higher self-esteem, and better communication skills among mentees. These programs may also benefit mentors, but these benefits have been understudied. More research is needed to determine the positive benefits of mentoring for mentors and mentees with similar learning characteristics, above and beyond positive benefits of mentorship in general.

Classic Hodgkin lymphoma (cHL) treatment paradigms are undergoing a shift with the integration of immune checkpoint inhibitors (ICIs) into both first-line and relapsed/refractory (R/R) regimens. In first-line therapy, the synergy between ICIs and chemotherapy may surpass the previous standards of ABVD and BV-AVD established by landmark trials including RATHL and ECHELON-1. In R/R disease, the combination of ICIs with chemotherapy has begun to challenge the paradigm of chemotherapy as a bridge to consolidative autologous stem cell transplantation. The clinical advances heralded by ICI offer unique challenges to management. ICI treatment and the associated inflammatory response can make the traditional timing and modalities of treatment response assessment difficult to interpret. In contrast to ABVD and BV-AVD, pembrolizumab-AVD results in PET2 positivity rates that are higher and less predictive of treatment response even when ultimate outcomes may be superior. This suggests that the predictive value of PET2 may be less reliable in the ICI era, prompting a reevaluation of response assessment strategies. Looking forward, circulating tumor DNA (ctDNA) may be a promising tool in response-adapted therapy. Its potential to complement or even supersede PET scans in predicting response to ICIs represents a critical advancement. The integration of ctDNA analysis holds the promise of refining response-adapted approaches and enhancing precision in therapeutic decision-making for patients with cHL. This review navigates the evolving landscape of cHL therapy, emphasizing the paradigmatic shift brought about by ICIs. This article explores the impact of combining ICIs with chemotherapy in both relapsed/refractory and first-line settings, scrutinizes the challenges posed to response-adapted therapy by ICIs, and highlights the potential role of ctDNA as an adjunct in refining response-adapted strategies for cHL.

Background:. High-volume pancreatic surgery centers require a significant investment in expertise, time, and resources to achieve optimal patient outcomes. A detailed understanding of the economics of major pancreatic surgery is limited among many clinicians and hospital administrators. A greater consideration of these financial aspects may in fact have implications for enhancing clinical care and for a broader sustainability of high-volume pancreatic surgery programs. Methods:. In this retrospective observational study, patients who underwent pancreaticoduodenectomy (PD), total pancreatectomy, or distal pancreatectomy at one academic medical center during the fiscal year 2021 were evaluated. Detailed hospital charges and professional fees were obtained for patients using the Qlik perioperative database. Clinical data for the study cohort were gathered from a prospectively maintained, IRB-approved pancreatic surgery database. Charges for the 91-day perioperative period were included. A P < 0.05 was considered significant. Results:. During the study period, 159 evaluable patients underwent 1 of 3 designated pancreatic resections included in the analysis. Ninety-seven patients (61%) were diagnosed with adenocarcinoma and 70% (n = 110) underwent PD. The total charges (combined professional and hospital charges) for the cohort encompassing the entire perioperative period were $20,661,759. The median charge per patient was $130,306 (interquartile range [IQR], $34,534). The median direct cost of care was $23,219 (IQR, $6321) and the median contribution margin per case was $10,092 (IQR, $22,949). The median surgeon professional fee charges were $7700 per patient (IQR, $1296) as compared to $3453 (IQR, $1,144) for professional fee receipts (45% of the surgeon charge). The differences between the professional fee charges and receipts per patient were also considerable for other health care professionals such as anesthesiologists ($4945 charges vs $1406 receipts [28%]) and pathologists ($3035 charges vs $680 receipts [22%]). The surgeon professional fees were only 6% of the total charges, while the professional fees for anesthesiology and pathology were 4% and 2% of the total charges, respectively. Supply charges were 3% of the total charges. Longer operative time was correlated with increased hospital and anesthesia charges, without a significant increase in surgeon charges (P < 0.001, P < 0.001, and P = 0.2, respectively). Male sex, diabetes, and low serum albumin correlated with greater total hospital charges (P = 0.01, P = 0.01, and P = 0.03, respectively). Conclusions:. The role of the surgeon in the perioperative clinical care of major pancreatic resection patients is crucial and important and is by no means limited to the operative day. Nevertheless, in the context of the current US health care system, the reimbursement to the surgeon in the form of professional fees is a relatively small fraction of the total health care receipts for these patients. This imbalance necessitates a substantial financial partnership between hospitals and their pancreatic surgery units to ensure the long-term viability of these programs.

ABSTRACTThe spread of hypervirulent (hv) and carbapenem-/multidrug-resistant Klebsiella pneumoniae is an emerging problem in healthcare settings. The New Delhi metallo-β-lactamase-1 (blaNDM-1) is found in Enterobacteriaceae including K. pneumoniae. The blaNDM-1 is capable of hydrolyzing β-lactam antibiotics which are used for treatment of severe infections caused by multidrug-resistant Gram-negative bacteria. This is associated with the unacceptably high mortality rate in immunocompromised burn injury patients. This study reports on the characterization of blaNDM-1 gene and virulence factors in hv carbapenem-/multidrug-resistant K. pneumoniae ST147 in the burns unit of a tertiary teaching hospital during routine surveillance. Two K. pneumoniae strains were obtained from wounds of burn-infected patients from May 2020 to July 2021. The hypervirulence genes and genetic context of the blaNDM-1 gene and mobile genetic elements potentially involved in the transposition of the gene were analyzed. We identified a conserved genetic background and an IS26 and open reading frame flanking the blaNDM-1 gene that could suggest its involvement in the mobilization of the gene. The plasmid harbored additional antibiotic resistance predicted regions that were responsible for resistance to almost all the routinely used antibiotics. To ensure the identification of potential outbreak strains during routine surveillance, investigations on resistance genes and their environment in relation to evolution are necessary for molecular epidemiology.IMPORTANCEData obtained from this study will aid in the prompt identification of disease outbreaks including evolving resistance and virulence of the outbreak bacteria. This will help establish and implement antimicrobial stewardship programs and infection prevention protocols in fragile health systems in countries with limited resources. Integration of molecular surveillance and translation of whole-genome sequencing in routine diagnosis will provide valuable data for control of infection. This study reports for the first time a high-risk clone K. pneumoniae ST147 with hypervirulence and multidrug-resistance features in Ghana.

Abstract Background The ability to detect the location of free-ranging sea turtles over time is desirable for ecological, conservation, and veterinary studies, but existing detection methods have limited sensitivity or longevity. Externally attached acoustic transmitters have variable, and sometimes short retention times for sea turtles. For several vertebrate taxa, surgically implanted acoustic transmitters have proven to be safe and effective for long-term detection; however, implanted transmitters have not yet been used for turtles. Results In this pilot study, INNOVASEA acoustic transmitters were surgically implanted subcutaneously in the pre-femoral region of fifteen hospitalized loggerhead sea turtles (Caretta caretta) that had been rehabilitated after stranding due to cold-stunning. Model V16-4H transmitters (estimated battery longevity = 2435 days) were implanted in turtles measuring ≥ 50 cm straight carapace length (SCL), and model V13-1H transmitters (estimated battery longevity = 1113 days) were implanted in turtles measuring 30–49 cm SCL. Incision healing was monitored over several months prior to release. Twelve turtles’ incisions healed without complication, on average, 55 days after surgery (median 47, range 41–100). Three turtles experienced incision complications, two of which healed after a second surgery, while the third required transmitter removal to promote healing. One of the fourteen implanted transmitters was confirmed to be dysfunctional prior to release, although it had been functional prior to implantation. To date, 100% of turtles released with functional acoustic transmitters (n = 13) have been detected a total of 915 times by 40 individual acoustic receivers off the coasts of Massachusetts, Rhode Island, New York, Virginia, North Carolina, and in southern New England offshore waters. Turtles with transmitters generated 5–235 detections (mean 70, median 43) on 1–13 individual acoustic receivers (mean 5, median 5) for periods of 3–400 days post-release (mean 118, median 87). Total detections and detection durations for these individuals are expected to increase over time due to anticipated transmitter battery longevity. Conclusions This study demonstrates that surgically implanted acoustic transmitters are effective for the detection of free ranging sea turtles, but refinement of surgical methodology is needed in light of the observed complications. Monitoring of healing is critical when evaluating novel surgical techniques in wildlife.

Abstract Functional annotation of open reading frames in microbial genomes remains substantially incomplete. Enzymes constitute the most prevalent functional gene class in microbial genomes and can be described by their specific catalytic functions using the Enzyme Commission (EC) number. Consequently, the ability to predict EC numbers could substantially reduce the number of un-annotated genes. Here we present a deep learning model, DeepECtransformer, which utilizes transformer layers as a neural network architecture to predict EC numbers. Using the extensively studied Escherichia coli K-12 MG1655 genome, DeepECtransformer predicted EC numbers for 464 un-annotated genes. We experimentally validated the enzymatic activities predicted for three proteins (YgfF, YciO, and YjdM). Further examination of the neural network’s reasoning process revealed that the trained neural network relies on functional motifs of enzymes to predict EC numbers. Thus, DeepECtransformer is a method that facilitates the functional annotation of uncharacterized genes.

The objectives of this study were to (1) investigate the association between human blood type and COVID-19 in both inpatient and longitudinal populations and (2) identify the association between blood type and severity of COVID-19 via presence of cellular biomarkers of severe infection in hospitalized individuals at our institution in South Florida. This study consisted of (1) a single-center retrospective analysis of 669 out of 2741 COVID-19-positive, screened patients seen from 1 January 2020 until 31 March 2021 at the University of Miami Emergency Department (ED) who tested positive for COVID-19 and had a documented ABO blood type and (2) a longitudinal SARS-CoV-2 immunity study (“CITY”) at the University of Miami Miller School of Medicine, consisting of 185 survey participants. In an inpatient setting, blood type appeared to be associated with COVID-19 severity and mortality. Blood type O sustained less risk of COVID-19 mortality, and blood type O- demonstrated less risk of developing COVID-19 pneumonia. Inpatients with O- blood type exhibited less biomarkers of severe infection than did other blood types. In a longitudinal setting, there was no association found between blood type and SARS-CoV-2 infection.