bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal malarial screening strategy in Australian blood donors: A cost‐effectiveness analysis
Authors: Cheng Qinglu , Hoad Veronica C. , Bentley Peter , Harley Robert , Schenberg Katia , Wiseman Virginia
Published: July 2024

Background and Objectives

The risk of transfusion‐transmitted malaria (TTM) infections is extremely low in Australia, and the cost‐effectiveness of the current screening strategy has not been assessed. This study aims to conduct a cost‐effectiveness analysis of different malaria screening strategies in blood donors as part of the risk‐based decision‐making framework.

Materials and Methods

A decision tree model was developed to assess the cost‐effectiveness of five alternative malaria screening strategies from a healthcare sector perspective. Screening strategies combining total or partial removal of malaria testing with different deferral periods were considered. The probabilities of developing severe and uncomplicated TTM were based on a literature review of cases in non‐endemic areas since 2000. The health outcomes were quantified using disability‐adjusted life years. The costs of non‐returning donors due to deferral were also included. Deterministic and probabilistic sensitivity analyses were conducted to account for data uncertainty.

Results

The residual risks for all strategies were so low that the costs, mortality and morbidity associated with TTM are almost negligible. The overall costs were predominantly influenced by the costs of non‐returning blood donors. As a result, removal of malaria testing and applying a 28‐day deferral for at‐risk donors were the least costly and most cost‐effective of all the options considered.

Conclusion

The current screening strategy for malaria in blood donors in Australia is not an efficient use of healthcare resources. Partial or total removal of malaria testing would bring significant cost savings without significantly compromising blood safety.
Graded control of Purkinje cell outputs by cAMP through opposing actions on axonal action potential and transmitter release
Authors: Furukawa Kei , Inoshita Takuma , Kawaguchi Shin‐ya
Published: July 2024

All‐or‐none signalling by action potentials (APs) in neuronal axons is pivotal for the precisely timed and identical size of outputs to multiple distant targets. However, technical limitations with respect to measuring the signalling in small intact axons have hindered the evaluation of high‐fidelity signal propagation. Here, using direct recordings from axonal trunks and/or terminals of cerebellar Purkinje cells in slice and culture, we demonstrate that the timing and amplitude of axonal outputs are gradually modulated by cAMP depending on the length of axon. During the propagation in long axon, APs were attenuated and slowed in conduction by cAMP via specifically decreasing axonal Na+ currents. Consequently, the Ca2+ influx and transmitter release at distal boutons are reduced by cAMP, counteracting its direct facilitating effect on release machinery as observed at various CNS synapses. Together, our tour de force functional dissection has unveiled the axonal distance‐dependent graded control of output timing and strength by intracellular signalling.

image

Key points

The information processing in the nervous system has been classically thought to rely on the axonal faithful and high‐speed conduction of action potentials (APs).

We demonstrate that the strength and timing of axonal outputs are weakened and delayed, respectively, by cytoplasmic cAMP depending on the axonal length in cerebellar Purkinje cells (PCs).

Direct axonal patch clamp recordings uncovered axon‐specific attenuation of APs by cAMP through reduction of axonal Na+ currents.

cAMP directly augments transmitter release at PC terminals without changing presynaptic Ca2+ influx or readily releasable pool of vesicles, although the extent is weaker compared to other CNS synapses.

Two opposite actions of cAMP on PC axons, AP attenuation and release augmentation, together give rise to graded control of synaptic outputs in a manner dependent on the axonal length.
Solid-State LiDAR With Optimized Dynamic Beam Power Intensity for Reduced Thermal Load
Authors: Lohan Danny J. , Dede Ercan M. , Schmalenberg Paul
Published: July 2024

Next generation sensor systems for automated vehicle navigation are likely to include light detection and ranging (LiDAR) sensors. Solid-state LiDAR technology that eliminates all mechanically moving parts is expected to enable compact and highly reliable operation. A challenge for such solid-state sensors is the thermal load generated by the on-chip light source, or laser, which includes power dissipated in the form of heat from additional integrated circuit components that are part of the full optoelectronics package. Here, we review possible thermal management strategies for a representative solid-state LiDAR package and focus on a programable scanning and beam intensity control technique for the sensor to enhance the thermal performance of the integrated light source. We demonstrate the impact of the proposed optimized beam scanning method in realizing a ~20% reduction in the device maximum temperature rise for the representative LiDAR sensor optoelectronics package when using a simplified forced air cooling solution. The method may be utilized for practical thermal management of sensors in a range of land-based navigational applications for automated vehicles or robotics.
Chromatin plasticity predetermines neuronal eligibility for memory trace formation
Authors: Santoni Giulia , Astori Simone , Leleu Marion , Glauser Liliane , Zamora Simon A. , Schioppa Myriam , Tarulli Isabella , Sandi Carmen , Gräff Johannes
Published: July 2024

Memories are encoded by sparse populations of neurons but how such sparsity arises remains largely unknown. We found that a neuron’s eligibility to be recruited into the memory trace depends on its epigenetic state prior to encoding. Principal neurons in the mouse lateral amygdala display intrinsic chromatin plasticity, which when experimentally elevated favors neuronal allocation into the encoding ensemble. Such chromatin plasticity occurred at genomic regions underlying synaptic plasticity and was accompanied by increased neuronal excitability in single neurons in real time. Lastly, optogenetic silencing of the epigenetically altered neurons prevented memory expression, revealing a cell-autonomous relationship between chromatin plasticity and memory trace formation. These results identify the epigenetic state of a neuron as a key factor enabling information encoding.
Asymmetric photoenzymatic incorporation of fluorinated motifs into olefins
Authors: Li Maolin , Yuan Yujie , Harrison Wesley , Zhang Zhengyi , Zhao Huimin
Published: July 2024

Enzymes capable of assimilating fluorinated feedstocks are scarce. This situation poses a challenge for the biosynthesis of fluorinated compounds used in pharmaceuticals, agrochemicals, and materials. We developed a photoenzymatic hydrofluoroalkylation that integrates fluorinated motifs into olefins. The photoinduced promiscuity of flavin-dependent ene-reductases enables the generation of carbon-centered radicals from iodinated fluoroalkanes, which are directed by the photoenzyme to engage enantioselectively with olefins. This approach facilitates stereocontrol through interaction between a singular fluorinated unit and the enzyme, securing high enantioselectivity at β, γ, or δ positions of fluorinated groups through enzymatic hydrogen atom transfer—a process that is notably challenging with conventional chemocatalysis. This work advances enzymatic strategies for integrating fluorinated chemical feedstocks and opens avenues for asymmetric synthesis of fluorinated compounds.
Policy-induced air pollution health disparities: Statistical and data science considerations
Authors: Mork Daniel , Delaney Scott , Dominici Francesca
Published: July 2024

Air pollution causes premature death and disease and disproportionately harms non-white and lower-income groups in the United States. Government policies are responsible for the racial disparity in air pollution exposure and related health outcomes. Investigating complex relationships between policies, air pollution, and health requires (i) harmonized data connecting policies, environmental exposures, socioeconomic characteristics, and health at the individual and area level; (ii) interpretable estimands accounting for the complex interplay between policies and disparities in exposures and health outcomes; and (iii) data science approaches that can elucidate direct and indirect policy effects on disparities to identify effective interventions. We review statistical considerations and new data science approaches needed to scrutinize the policy impacts on disparities in air pollution exposure and health outcomes.
The sugar cube: Network control and emergence in stereoediting reactions
Authors: Carder Hayden M. , Occhialini Gino , Bistoni Giovanni , Riplinger Christoph , Kwan Eugene E. , Wendlandt Alison E.
Published: July 2024

Stereochemical editing strategies have recently enabled the transformation of readily accessible substrates into rare and valuable products. Typically, site selectivity is achieved by minimizing kinetic complexity by using protecting groups to suppress reactivity at undesired sites (substrate control) or by using catalysts with tailored shapes to drive reactivity at the desired site (catalyst control). We propose “network control,” a contrasting paradigm that exploits hidden interactions between rate constants to greatly amplify modest intrinsic biases and enable precise multisite editing. When network control is applied to the photochemical isomerization of hexoses, six of the eight possible diastereomers can be selectively obtained. The amplification effect can be viewed as a mesoscale phenomenon between the limiting regimes of kinetic control in simple chemical systems and metabolic regulation in complex biological systems.
The first fossil collectors
Dinosaurs at the Dinner Party
Edward Dolnick
Scribner, 2024. 352 pp.
Authors: Nieuwland Ilja
Published: July 2024

A lively tour of paleontology’s early days fails to coalesce into a coherent narrative
In Other Journals
Authors: Smith Jesse , Sofowora Iyinoluwa , Hurtley Stella M. , Ross Sarah H. , Simonti Corinne , Stajic Jelena
Published: July 2024

Editors’ selections from the current scientific literature
Little-known virus surging in Latin America may harm fetuses
Authors: Moutinho Sofia
Published: July 2024

Oropouche virus could be linked to brain malformation and stillbirths, Brazilian health officials say
Timely cholecystectomy: important factors to improve guideline adherence and patient treatment
Authors: Fehring Leonard , Brinkmann Hendrik , Hohenstein Sven , Bollmann Andreas , Dirks Patrick , Pölitz Jörg , Prinz Christian
Published: July 2024

Objective

Cholecystectomy is one of the most frequently performed surgeries in Germany and is performed as a treatment of acute cholecystitis (guideline S3 IIIB.8) and after endoscopic retrograde cholangiopancreatography for choledocholithiasis with simultaneous cholecystolithiasis (guideline S3 IIIC.6). This article examines the effects of a guideline update from 2017, which recommends prompt cholecystectomy within 24 hours of admission due to cholecystitis or within 72 hours after bile duct repair. In addition, it aims to identify reasons (eg, financial disincentives) and potential for improvement for non-adherence to the guidelines.

Design

Methodologically, a retrospective analysis based on routine billing data from 84 Helios Group hospitals from 2016 and 2022, with a total of 45 393 included cases, was applied. The guideline adherence rate is used as the main outcome measure.

Results

Results show the guideline updates led to a statistically significant increase in the proportion of cholecystectomy performed in a timely manner (guideline S3 IIIB.8: increase from 43% to 49%, p<0.001; guideline S3 IIIC.6: increase from 7% to 20%, p<0.001). Medical, structural and financial reasons for non-adherence could be identified.

Conclusion

As possible reasons for non-adherence, medical factors such as advanced age, multimorbidity and frailty could be identified. Analyses of structural factors revealed that hospitals in very rural regions are less likely to perform timely cholecystectomies, presumably due to infrastructural and personnel-capacity bottlenecks. A similar picture emerges for maximum-care hospitals, which might be explained by more severe and complex cases on average. Further evaluation indicates that an increase in and better hospital-internal participation of gastroenterologists in remuneration could lead to even greater adherence to the S3 IIIC.6 guideline.
Improving triage in upper gastrointestinal bleeding: insights from the UK National Endoscopy Database (NED)
Authors: Beaton David , Sharp Linda , Trudgill Nigel John , Rutter Matt
Published: July 2024

Background and aims

We aimed to analyse data from the UK National Endoscopy Database (NED) to investigate factors associated with endotherapy in patients with suspected upper gastrointestinal bleeding (UGIB) .

Methods

Analysis of oesophagogastroduodenoscopy (OGD) uploads to the NED from 1 March 2019 to 29 February 2020 was performed. UGIB was defined as procedures with indications of melaena and/or haematemesis. The proportion where endotherapy was performed was calculated. Mixed-effects logistic regression was performed with patient sex, patient age, type of admission (inpatient, outpatient, unclassified) and symptoms as fixed effects on the dependent variable (receipt of endotherapy). Results were presented as adjusted ORs (aORs) with 95% CIs.

Results

47 481 OGDs were performed for UGIB; endotherapy was performed in 14.8%, increasing to 20.0% when only inpatient OGDs were analysed. Patients aged 18–39 years were half as likely to undergo endotherapy than those aged 50–59 years (aOR 0.5, 95% CI 0.5 to 0.6), with male patients at higher risk than females (aOR 1.3, 95% CI 1.2 to 1.4).

Patients with both melaena and haematemesis were nearly three times more likely to receive endotherapy (aOR 2.8, 95% CI 2.6 to 3.0) compared with those with melaena alone. Conversely, patients with only haematemesis had a lower risk than those with melaena alone (aOR 0.9, 95% CI 0.8 to 0.9).

Conclusions

Younger and female patients were at lower risk of undergoing endotherapy, while patients with both melaena and haematemesis were at three times the risk as those with each symptom alone. Incorporating these findings into UGIB risk scores could improve patient triage.
Long-term sustainability of response to upadacitinib among patients with active rheumatoid arthritis refractory to biological treatments: results up to 5 years from SELECT-BEYOND
Authors: van Vollenhoven Ronald F , Hall Stephen , Wells Alvin F , Meerwein Sebastian , Song Yanna , Tanjinatus Oishi , Fleischmann Roy
Published: July 2024

Objective

To evaluate the long-term sustainability of response to the Janus kinase inhibitor upadacitinib among patients with rheumatoid arthritis and an inadequate response or intolerance to biological disease-modifying antirheumatic drugs (bDMARD-IR) in the SELECT-BEYOND phase 3 trial.

Methods

Patients on background conventional synthetic DMARDs (csDMARDs) were treated once daily with upadacitinib 15 mg or placebo. Patients who completed the week 24 visit could enter a long-term extension of up to 5 years. The sustainability of response was assessed based on achievement of Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and Disease Activity Score 28-joint count using C-reactive protein (DAS28 (CRP)) targets and evaluated up to week 260 in all patients receiving the approved upadacitinib 15 mg dose, including those randomised to upadacitinib 15 mg and those who switched from placebo to upadacitinib 15 mg at week 12.

Results

In this bDMARD-IR population, 45% (n=104/229) and 79% (n=172/219) of patients treated with upadacitinib 15 mg plus background csDMARD(s) achieved CDAI remission or CDAI low disease activity (LDA) at any point during the 5-year study, respectively. Of those who achieved CDAI remission/LDA, 25%/43% maintained their initial response through 240 weeks of follow-up after first achieving response. Most patients who lost remission or LDA were able to recapture that response by the cut-off date. Similar overall results were observed for SDAI and DAS28 (CRP). No strong predictors of response were identified.

Conclusions

Over three-quarters of bDMARD-IR patients achieved CDAI LDA with upadacitinib, and almost half of those maintained LDA through 240 weeks of follow-up. Remission was achieved by nearly half of all patients and maintained in approximately a quarter of those achieving remission.

Trial registration number

NCT02706847.
A level-depth correspondence between fusion rings of loop groups and subfactors
Authors: Yang Jun
Published: July 2024

Given fusion categories of loop group representations at level [Formula: see text], we construct subfactors [Formula: see text] of depth [Formula: see text] which satisfy the following conditions : (1) [Formula: see text] for type [Formula: see text] and [Formula: see text] for the other types with [Formula: see text] uniquely determined by the type. (2) The fusion ring of the associated bimodules is isomorphic to the one of loop group at level [Formula: see text].
Cofiniteness of generalized local cohomology modules over local rings
Authors: Tri Nguyen Minh
Published: July 2024

Let [Formula: see text] be a local commutative Noetherian ring and [Formula: see text] an ideal of [Formula: see text] Assume that [Formula: see text] is a finitely generated [Formula: see text]-module of finite projective dimension [Formula: see text] and [Formula: see text] is a finitely generated [Formula: see text]-module of dimension [Formula: see text] We prove that [Formula: see text] is Artinian. Moreover, if [Formula: see text] is finitely generated, then [Formula: see text] is an [Formula: see text]-cofinite [Formula: see text]-module.
Management Challenges and Potential Malabsorption of Valproic Acid in a Patient with Bipolar Disorder and Gastrointestinal History
Authors: Kwok James , Wong Janeline , Kim Kye
Published: July 2024

Bipolar disorder is a chronic psychiatric condition typically managed using mood stabilizers such as valproic acid, lithium, and atypical antipsychotics, the former which is absorbed in the gastrointestinal tract. This case report presents the challenges encountered in managing bipolar disorder in a patient with a history of extensive gastrointestinal (GI) issues. The patient was initially treated with lithium but experienced adverse effects, prompting a switch to valproic acid (VPA) tablets. However, due to ongoing GI problems unrelated to her medication and to help improve tolerability, the patient underwent multiple medication formulation changes, including Depakote delayed release tablets, Depakene liquid, and Depakote sprinkle capsules. However, the patient’s VPA levels decreased below therapeutic levels after the formulation changes despite medication compliance. This case highlights the importance of considering GI issues in optimization of a treatment plan for patients with bipolar disorder.
Assessing the Impact of Climate Change on Agricultural Water Management in Mainland Southeast Asia
Authors: Amnuaylojaroen Teerachai , Limsakul Atsamon , Chanvichit Pavinee
Published: July 2024

This study aims to address an assessment of climate change’s impact on agricultural water management in mainland Southeast Asia (MSEA). We used several agroclimatic indices, such as consecutive dry days (CDDs), maximum number of consecutive wet days (CWDs), consecutive summer days (CSUs), cold spell duration index (CDSIs), and warm and wet days (WWs), based on the Geophysical Fluid Dynamics Laboratory Earth System Model to characterize the effect of climate on crop water need (CWN) in MSEA. The climate model shows monthly precipitation and temperature patterns with acceptable accuracy but with an underestimation of precipitation and a warm bias in temperature. CDDs show a significant increase in aridity and drought occurrences, particularly in northern Myanmar, Laos, Vietnam, and northern Thailand, across different representative concentration pathways. CSUs have been seen to have a substantial influence on the region’s agricultural economy. The CDSIs, on the other hand, show a decrease in the duration of cold spells, indicating the existence of milder climatic conditions that could potentially affect crop growth. The CWDs show a decreasing trend in most of the multiple regions in Thailand, Laos, Vietnam, Cambodia, and Malaysia. Though the WW index shows more wet days, this does not immediately imply improved crop growth; rather, it highlights possible changes in water availability that could affect agricultural practices. While negative CWNs in the dry season months like March and November suggest possible water shortages, which pose risks to agriculture and food security in Myanmar, northern and eastern Thailand, and Cambodia, especially at the end of the century, increases in CWNs during the rainy season correspond with anticipated higher water demands for agriculture.
Compact 8‐Port Low‐Profile Antenna Array for 5G Mobile Phones
Authors: Chen Hongtao , Zhou Hui , Jin Hang , Yuan Chenghao , Fang Yanqun , Zhu Mingmin , Yu Guoliang , Qiu Yang , Zhou Hao-Miao
Published: July 2024

A compact eight‐element frame antenna array covering the 5G n79 frequency band (4.4–5.0 GHz) has been proposed in this paper. Considering the demands in the application of 5G ultrathin smartphones, the antenna unit has been miniaturized and designed with a low profile. Each antenna unit occupies a distance of 11.1 mm on the long edge, and the profile height of each unit is only 3 mm. The antenna array consists of 8 identical monopole antennas. By loading an inverted E‐shaped slot on the ground plane and arranging the positions of the antenna units reasonably without the need for a decoupling structure, the antenna can achieve a low profile and compact design. Simultaneously, it can achieve excellent isolation and cover the entire n79 frequency band. The processed eight‐element antenna array has a −6 dB bandwidth ranging from 4.38 to 5.19 GHz. The isolation between all antennas is better than −13.9 dB. The total efficiency is between 48.66% and 90.57%, with an average efficiency of 68.6%. The ECC (envelope correlation coefficient) is less than 0.066. The antenna array is characterized by its small size, low profile, simple structure, easy manufacturing, and excellent radiation performance. It holds significant application value in the design of MIMO antennas for 5G ultrathin smartphones.
mTOR Deletion Alleviates CD4+ T‐Cell Dysfunction in Sepsis through Reducing CTLA4 Accumulation Mediated by Rescuing Autophagy
Authors: Lei Xianli , Zhao Guoyu , Xie Yawen , Cui Na
Published: July 2024

Sepsis has been the leading cause of death in ICU patients. CD4+ T cells are the mainstay of the body’s immune system, and the depletion of CD4+ T cells in sepsis is of great concern. Cytotoxic T lymphocyte‐associated protein 4 (CTLA4) is a negative immunomodulator for T cell activation and degradation through the autophagy‐lysosome pathway. Mammalian target of rapamycin (mTOR) is the most classical upstream regulator of autophagy. With a mouse model of sepsis through cecal ligation and puncture (CLP), T cell specific‐mTOR/tuberous sclerosis complex 1 (TSC1)‐knockout mice, and bafilomycin A1, a specific autophagosome‐lysosome (A‐L) fusion inhibitor, we primarily proved that mTOR could modulate the expression and accumulation of CTLA4 by regulating the onset process of autophagy such as A‐L fusion. Given such a regulatory relationship, targeting mTOR could provide new light to improve immune function in sepsis, and the prospect of using rapamycin in the clinic would be worth exploring further.
Navigation‐Assisted One‐Stage Total Knee Arthroplasty With Extra‐Articular Corrective Osteotomy for Knee Osteoarthritis With Femoral and Tibial Extra‐Articular Deformity: A Case Report
Authors: Kubo Mitsuhiko , Hirobe Sho , Maeda Tsutomu , Kumagai Kosuke , Amano Yasutaka , Nosaka Yuki , Hasegawa Takahide , Imai Shinji
Published: July 2024

Background: Knee osteoarthritis (OA) with extra‐articular deformity (EAD) is a rare condition for which achieving accurate alignment with total knee arthroplasty (TKA) is difficult. Extra‐articular corrective osteotomy may be necessary for severe deformities.

Case Presentation: A 76‐year‐old man underwent TKA for knee OA with EAD due to malunion after fractures of the femur and tibia. The femoral varus and the tibial valgus/recurvatum deformities were mild and corrected by intra‐articular osteotomy using navigation (i.e., navigation‐assisted standard TKA). However, the femoral antecurvatum deformity was severe, and we performed extra‐articular corrective osteotomy simultaneously with TKA. Navigation was used not only for TKA but also for extra‐articular corrective osteotomies. The osteotomy site was fixed with a cemented stem and metaphyseal sleeve. The postoperative hip–knee–ankle angle was 1° varus, the femoral implant was implanted at 0.5° varus/0.5° flexion, and the tibial implant was implanted at 0.5° varus/0° posterior slope. Two years after surgery, improvements were obtained in the range of motion from 15°–95° to 0°–110°, the Knee Society Score from 39 to 92 points, and the functional score from 35 to 100 points.

Conclusions: One‐stage TKA with extra‐articular corrective osteotomy achieved good clinical results due to accurate alignment using navigation and firm fixation of the osteotomy site using cemented‐stem and metaphyseal sleeve without any fixation devices.
Antiallergic Effect of the Alpha‐Cyclodextrin Moringin Complex in Rat Basophilic Leukaemia (RBL‐2H3) Cell Line
Authors: Yousef A. Alnakeeb Ebtisam , Abdull Razis Ahmad Faizal , Wei Chan Kim , Ling Tham Chau , Han Chan Yee , Kalifa Kafo Anwar Salm , Jambari Nuzul Noorahya , Rollin Patrick , Djedaini-Pilard Florence
Published: July 2024

Allergic diseases (ADs) are a major concern when it comes to public well‐being. Moringa oleifera Lam is a tropical plant that is used in traditional medicine due to the presence of isothiocyanate. The present study investigated the antiallergic properties of 4‐(α‐L‐rhamnopyranosyloxy)‐benzyl isothiocyanate or moringin isolated from Moringa oleifera seeds in the form of alpha‐cyclodextrin‐moringin (α‐CD/MG) complex on rat basophilic leukaemia (RBL‐2H3) cell line at both the early and late stages of an allergic reaction. The α‐CD/MG complex was initially elucidated using nuclear magnetic resonance (NMR) followed by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium inner salt proliferation assay to evaluate the cytotoxicity and cell viability with respect to ketotifen fumarate (KF) and α‐CD/MG. The release of beta‐hexosaminidase (β‐hexosaminidase) and histamine was used to determine the level of inhibition in the early stage while the suppression of the release of prostaglandin (PGD2), tumour necrosis factor‐alpha (TNF‐α), and interleukin (IL‐4) was considered in the late stage. Higher concentrations of α‐CD/MG (5 μM, p < 0.001) in mast cell degranulation significantly inhibited the expression of β‐hexosaminidase, histamine, TNF‐α, PGD2, and IL‐4 in both the early and late stages. Thus, α‐CD/MG can potentially be developed as an antiallergic drug as it has the ability to inhibit allergic responses in the late and early stages.
A Novel Rat Infant Model of Medial Temporal Lobe Epilepsy Reveals New Insight into the Molecular Biology and Epileptogenesis in the Developing Brain
Authors: Wormuth Carola , Papazoglou Anna , Henseler Christina , Ehninger Dan , Broich Karl , Haenisch Britta , Hescheler Jürgen , Köhling Rüdiger , Weiergräber Marco
Published: July 2024

Although several adult rat models of medial temporal lobe epilepsy (mTLE) have been described in detail, our knowledge of mTLE epileptogenesis in infant rats is limited. Here, we present a novel infant rat model of mTLE (InfRPil‐mTLE) based on a repetitive, triphasic injection regimen consisting of low‐dose pilocarpine administrations (180 mg/kg. i.p.) on days 9, 11, and 15 post partum (pp). The model had a survival rate of >80% and exhibited characteristic spontaneous recurrent electrographic seizures (SRES) in both the hippocampus and cortex that persisted into adulthood. Using implantable video‐EEG radiotelemetry, we quantified a complex set of seizure parameters that demonstrated the induction of chronic electroencephalographic seizure activity in our InfRPil‐mTLE model, which predominated during the dark cycle. We further analyzed selected candidate genes potentially relevant to epileptogenesis using a RT‐qPCR approach. Several candidates, such as the low‐voltage‐activated Ca2+ channel Cav3.2 and the auxiliary subunits β1 and β2, which were previously reported to be upregulated in the hippocampus of the adult pilocarpine mTLE model, were found to be downregulated (together with Cav2.1, Cav2.3, M1, and M3) in the hippocampus and cortex of our InfRPil‐mTLE model. From a translational point of view, our model could serve as a blueprint for childhood epileptic disorders and further contribute to antiepileptic drug research and development in the future.
Supplementary Video S2 from DINC 2.0: A New Protein–Peptide Docking Webserver Using an Incremental Approach
Authors: Antunes Dinler A. , Moll Mark , Devaurs Didier , Jackson Kyle R. , Lizée Gregory , Kavraki Lydia E.
Published: July 2024

Cross-docking with DINC. Narrated screencast demonstrating how to run cross-docking experiments with DINC 2.0 (i.e., when the ligand coordinates and conformation do not correspond to that of the ligand co-crystallized in the receptor binding site). This video tutorial demonstrates how to define specific values for "grid center" and "grid size", and how to visualize the corresponding "grid box" using the AutoDockTools software. Three different complexes are used in this tutorial (PDB codes 1OHR, 4Q5M and 1SKJ).
Supplementary Video S1 from Integrating DNA Methylation and Hydroxymethylation Data with the Mint Pipeline
Authors: Cavalcante Raymond G. , Patil Snehal , Park Yongseok , Rozek Laura S. , Sartor Maureen A.
Published: July 2024

This video provides the biological motivation for developing the mint pipeline, and we walk the user through the installation process and setting up the computing environment to run the pipeline.
Data from DINC 2.0: A New Protein–Peptide Docking Webserver Using an Incremental Approach
Authors: Antunes Dinler A. , Moll Mark , Devaurs Didier , Jackson Kyle R. , Lizée Gregory , Kavraki Lydia E.
Published: July 2024

Abstract
Molecular docking is a standard computational approach to predict binding modes of protein–ligand complexes by exploring alternative orientations and conformations of the ligand (i.e., by exploring ligand flexibility). Docking tools are largely used for virtual screening of small drug-like molecules, but their accuracy and efficiency greatly decays for ligands with more than 10 flexible bonds. This prevents a broader use of these tools to dock larger ligands, such as peptides, which are molecules of growing interest in cancer research. To overcome this limitation, our group has previously proposed a meta-docking strategy, called DINC, to predict binding modes of large ligands. By incrementally docking overlapping fragments of a ligand, DINC allowed predicting binding modes of peptide-based inhibitors of transcription factors involved in cancer. Here, we describe DINC 2.0, a revamped version of the DINC webserver with enhanced capabilities and a more user-friendly interface. DINC 2.0 allows docking ligands that were previously too challenging for DINC, such as peptides with more than 25 flexible bonds. The webserver is freely accessible at http://dinc.kavrakilab.org, together with additional documentation and video tutorials. Our team will provide continuous support for this tool and is working on extending its applicability to other challenging fields, such as personalized immunotherapy against cancer. Cancer Res; 77(21); e55–57. ©2017 AACR.
Data from DeepPhe: A Natural Language Processing System for Extracting Cancer Phenotypes from Clinical Records
Authors: Savova Guergana K. , Tseytlin Eugene , Finan Sean , Castine Melissa , Miller Timothy , Medvedeva Olga , Harris David , Hochheiser Harry , Lin Chen , Chavan Girish , Jacobson Rebecca S.
Published: July 2024

Abstract
Precise phenotype information is needed to understand the effects of genetic and epigenetic changes on tumor behavior and responsiveness. Extraction and representation of cancer phenotypes is currently mostly performed manually, making it difficult to correlate phenotypic data to genomic data. In addition, genomic data are being produced at an increasingly faster pace, exacerbating the problem. The DeepPhe software enables automated extraction of detailed phenotype information from electronic medical records of cancer patients. The system implements advanced Natural Language Processing and knowledge engineering methods within a flexible modular architecture, and was evaluated using a manually annotated dataset of the University of Pittsburgh Medical Center breast cancer patients. The resulting platform provides critical and missing computational methods for computational phenotyping. Working in tandem with advanced analysis of high-throughput sequencing, these approaches will further accelerate the transition to precision cancer treatment. Cancer Res; 77(21); e115–8. ©2017 AACR.
Assistir em casa: presença das tecnologias audiovisuais e consumo no ambiente doméstico
Authors: Debiasi Carlos Alberto , Silveira Luciana Martha
Published: July 2024

The presence of audiovisual artifacts in domestic environment creates different living habits. This study reflects on domestic audiovisual consumption relations during the COVID-19 pandemic. This period made the private environment more relevant and changed habits. This research explains this processes by ethnographies of reception and cultural studies theories. Information was collected by a questionnaire and interviews with residents of Curitiba, Brazil, about their television and streaming consumption habits. The pandemic changed family and spatial arrangements in the collected sample but some habits related to earlier uses remained throughout that process.
El dispositivo Oslo
Authors: Cumsille Kamal
Published: July 2024

El presente artículo plantea que Oslo, en lugar de ser un proceso de paz, es un dispositivo (en el sentido de Foucault), puesto que, en lugar de buscar una solución para el problema colonial de Palestina, lo que hace en realidad es introducir en la región y en el caso palestino en particular, las nuevas lógicas de gobierno y economía desplegadas en el contexto de la postguerra Fría desde el pensamiento estratégico estadounidense como nuevas racionalidades imperantes. Esto vendría a sumar a la lógica necropolítica de la ocupación colonial de Palestina, la lógica de la gubernamentalidad (según la definió Foucault), en la medida en que, omitiendo la búsqueda palestina de la liberación nacional, Oslo introdujo la transformación del movimiento nacional palestina en una policía y un gobierno democrático, junto con la obligación de la cooperación económica con Israel a nivel local y regional.
Palestina no contexto do colonialismo
Authors: Teles Bárbara Caramuru , Othman Helena de Morais Manfrinato
Published: July 2024

A Antropologia, em suas primeiras décadas, se dedicou a discussões sobre os temas do parentesco, religião, alteridade, natureza e cultura, indivíduo e sociedade, métodos e ao fazer etnográfico, discussões que viriam a se tornar canônicas na disciplina. Suas metáforas holistas (Strathern, 2017: 345) preocupadas com a integridade e coesão que compõem o vernáculo acadêmico - sociedade, sistema, cultura -, nasceram das etnografias realizadas em contextos coloniais, em que antropólogos se viram ansiosos com o temor do desaparecimento dos modos de vida locais. Nossa Antropologia nasceu, como afirma Talal Asad (2017), com o pecado original do colonialismo, com análises “produzidas por europeus para audiências europeias – de sociedades não europeias dominadas pelo poder europeu” (Asad, 2017: 320) que operam tanto em nossa teoria quanto prática etnográfica. O autor chama atenção para o fato, porém, que há uma estranha relutância de antropólogos a admitir as estruturas de poder em que essa ciência foi formada.
Integrative Metabolomics Differentiate Coronary Artery Disease, Peripheral Artery Disease, and Venous Thromboembolism Risks
Authors: Lee Jiwoo , Gilliland Thomas C. , Dron Jacqueline , Koyama Satoshi , Nakao Tetsushi , Lannery Kim , Wong Megan , Peloso Gina M. , Hornsby Whitney E. , Natarajan Pradeep
Published: July 2024

BACKGROUND:

Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating underlying mechanisms may shed light on disease mechanisms. In this study, we aimed to identify (1) epidemiological and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE.

METHODS:

We used metabolomic data from 95 402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease. Cox proportional-hazards models estimated the associations of 249 metabolites with incident disease. Bidirectional 2-sample Mendelian randomization (MR) estimated the causal effects between metabolites and outcomes using genome-wide association summary statistics for metabolites (n=118 466 from the UK Biobank), CAD (n=184 305 from CARDIoGRAMplusC4D 2015), PAD (n=243 060 from the Million Veterans Project), and VTE (n=650 119 from the Million Veterans Project). Multivariable MR was performed in subsequent analyses.

RESULTS:

We found that 196, 115, and 74 metabolites were associated (
P
<0.001) with CAD, PAD, and VTE, respectively. Further interrogation of these metabolites with MR revealed 94, 34, and 9 metabolites with potentially causal effects on CAD, PAD, and VTE, respectively. There were 21 metabolites common to CAD and PAD and 4 common to PAD and VTE. Many putatively causal metabolites included lipoprotein traits with heterogeneity across different sizes and lipid subfractions. Small VLDL (very-low-density lipoprotein) particles increased the risk for CAD while large VLDL particles decreased the risk for VTE. We identified opposing directions of CAD and PAD effects for cholesterol and triglyceride concentrations within HDLs (high-density lipoproteins). Subsequent sensitivity analyses including multivariable MR revealed several metabolites with robust, potentially causal effects of VLDL particles on CAD.

CONCLUSIONS:

While common vascular conditions are associated with overlapping metabolomic profiles, MR prioritized the role of specific lipoprotein species for potential pharmacological targets to maximize benefits in both arterial and venous beds.
Revision of Vitruvius (Hemiptera: Heteroptera: Pentatomidae) with the description of a new species from Cambodia and Thailand
Authors: ROCA-CUSACHS MARCOS , RIDER DAVID A. , KMENT PETR , JUNG SUNGHOON
Published: July 2024

The monotypic Oriental genus Vitruvius Distant, 1901 (Hemiptera: Heteroptera: Pentatomidae: Pentatominae), having an intricate and confusing taxonomic history, is revised. A new species, Vitruvius dobby Roca-Cusachs, Rider & Kment new species, is described from Cambodia and Thailand. Notes on the hypothesized classification of the genus based on both biology and morphology are presented, but its systematic placement is left unresolved. The morphological characteristics of the genus are redescribed. Habitus photographs of the type specimen of V. insignis Distant, 1901 and its labels, and photographs of both the species are provided.
Assessing Strengths and Well-Being in Primary Care for Adolescents With Mental Health and Substance Use Concerns
Authors: Singh Deepinder , Schumacher Heidi K. , Pellegrino Christine A. , Holmes Breena W. , Garfield Rachel L. , Harder Valerie S.
Published: July 2024

As the COVID-19 pandemic highlighted gaps in meeting adolescent behavioral health needs, primary care providers (PCPs) were a locus for interventions to address adolescent mental health and substance use concerns. Strength-based approaches may support PCP promotion of positive behavioral health in adolescents, but competing priorities or other factors may inhibit their use. We analyzed health record review data from 31 primary care practices to assess utilization of strength-based approaches during the health supervision visit (HSV) for adolescents with and without behavioral health concerns. We found that most had strengths identified (78%) or well-being topics addressed (83%). However, adolescents screening positive for depression were 40% less likely to have strengths identified, whereas those screening positive for anxiety or substance use were 89% and 163%, respectively, more likely to have well-being topics addressed. Primary care providers may need support for integrating strength-based approaches when managing adolescents screening positive for depression.
Liturgical Formation through Ecumenical Experiences:Insights from Inter-University and Inter-Confessional Lectures
Authors: Schweyer Stefan
Published: July 2024

Ecumenism serves to promote communion between Christian groups. In this paper I will discuss how the transposition of this principle in the university setting has shown to be effective in liturgical formation among university students. The thesis of the article is as follows: Ecumenical learning can be fostered by combining reflective, relational, and experiential learning methods. The implementation of ecumenical learning in the university setting has been shown to provide three constructive outcomes: (1) It facilitates the sharing of liturgical gifts by offering an environment in which the exchange of gifts can take place, (2) it strengthens ecumenical awareness, and (3) it fosters mutual appreciation.
The ‘pathologically state dependent’ versus ‘middle-aged ministers on mammoth salaries’: The legitimation contest over a 2013 austerity measure in the Republic of Ireland
Authors: Gaffney Stephen
Published: July 2024

This paper provides a discourse analysis of the political and media debate surrounding a 2013 austerity measure that targeted unemployed young people in the Republic of Ireland. Applying Van Leeuwen’s ‘justificatory schema’ it reveals the legitimation of this measure relied on an ‘anti-welfare populist’ framing of the young unemployed as ‘welfare dependent’ and thus ‘undeserving’. Furthermore, this analysis finds that those opposed to this austerity measure sought to de-legitimate it and to re-legitimate the young unemployed. At times by singling out alternative ‘undeserving’ figures to be targeted with austerity in their place. This process thus remained open to contestation and resignification, albeit in a manner that failed to challenge the underlying political-economic logic at play. The antagonistic framings revealed by these findings complicate the emphasis on ‘de-politicisation’ in the pre-existing literature using discourse analysis methods to investigate the legitimation of austerity.
Antimicrobial Activities of a New Alkaloid from Marine-Derived Fungus, Penicillium sp. OM01
Authors: Pham Van Cuong , Nguyen Thi Hue , Nguyen Thuy Linh , Nguyen Mai Anh , Vu Thi Quyen , Vu Thi Thu Huyen , Le Thi Hong Minh , Huong Doan Thi Mai
Published: July 2024

Objectives

This study focused on the isolation, structural elucidation, and antimicrobial activities of compounds from the culture broth of the strain Penicillium sp. OM01 (isolated from the marine mollusk sample Spondylus squamosus (Schreibers, 1793)).

Methods

Various chromatographic methods were used to isolate compounds from the ethyl acetate and MeOH extracts of the strain Penicillium sp. OM01. Their structures were elucidated using HR-ESI-MS and NMR data. The compounds were evaluated for antimicrobial effects using the dilution turbidimetric broth method.

Results

One new alkaloid, penicritin (1), together with seven known compounds, including phenol A acid (2), topsentisteron D3 (3), ergostanol (4), (22 E,24 R)-24-methylcholesta-5,22-diene-3 β, 7 β-diol (5), 5 α,6 α-epoxy-(22 E,24 R)-ergosta-8,22-diene-3 β,7 α-diol (6), staphylopeptide A (7), and 4-hydroxybenzoic acid (8) were isolated from the culture broth of the marine-derived fungus Penicillium sp. OM01. Compounds 2-4 and 6 exhibited antibacterial activity against Gram-(+) bacteria, Enterococcus faecalis, Staphylococcus aureus, Bacillus cereus, and yeast Candida albicans with MIC values ranging from 32 to 256 µg/mL.

Conclusions

This is the first report of the strain Penicillium sp. OM01 from the marine mollusk sample S. squamosus (Schreibers, 1793). One new and seven known compounds were isolated from the strain Penicillium sp. OM01 (isolated from the marine mollusk sample S. squamosus (Schreibers, 1793). Compound 4 is a potential antibacterial agent.
Applying Market Basket Analysis to Determine Complex Coassociations Among Food Allergens in Children With Food Protein-Induced Enterocolitis Syndrome (FPIES)
Authors: Banerjee Ankona , Nobleza Kenneth , Haddad Cynthia , Eubanks Joshua , Rana Ruchit , Rider Nicholas L. , Pompeii Lisa , Nguyen Duc , Anvari Sara
Published: July 2024

Background

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy, characterized by delayed onset of repetitive vomiting occurring 1 to 4 h following ingestion of a food allergen. Managing FPIES requires strict avoidance of the food trigger. The concern with FPIES is determining the risk of another FPIES food trigger reaction due to potential coassociations with other foods or food groups. An effective statistical approach for analyzing FPIES-related data is essential to identify common coallergens and their associations.

Methods

This study employed Market Basket Analysis, a data-mining technique, to examine correlations and patterns among allergens in FPIES patients at a Houston, Texas, pediatric tertiary center. A retrospective analysis of electronic medical records from January 2018 to March 2022 for allergist diagnosed FPIES patients was conducted. The analysis utilized R software, specifically the “arules” and “arulesViz” packages, implementing the Apriori algorithm with set minimum support and confidence thresholds.

Results

The study included 210 FPIES cases over 4 years, with 112 patients reacting to one food trigger and 98 to more than one trigger. In the latter group, the 5 predominant triggers were cow's milk (45.9%), rice (31.6%), oats (30.6%), soy (22.4%), and avocado (19.4%). Market Basket Analysis identified significant associations between food categories, particularly between soy and dairy, egg and dairy, oat and dairy, rice and dairy, and avocado and dairy.

Conclusion

Market Basket Analysis proved effective in identifying patterns and associations in FPIES data. These insights are crucial for healthcare providers in formulating dietary recommendations for FPIES patients. This approach potentially enhances guidance on food introductions and avoidances, thereby improving management and the quality of life for those affected by FPIES.