bluuebunny/crossref_metadata_2025 huggingface dataset:
Orlicz functions that do not satisfy the Δ₂-condition and high order Gâteaux smoothness in ℎ_{𝑀}(Γ)
Authors: Ivanov Milen , Troyanski Stanimir , Zlateva Nadia
Published: October 2023

We study Orlicz functions that do not satisfy the

Δ
2

\Delta _2

-condition at zero. We prove that for every Orlicz function

M
M

such that

lim sup

t
→
0

M
(
t
)

/

t
p

>
0

\limsup _{t\to 0}M(t)/t^p \!>0

for some

p
≥
1

p\ge 1

, there exists a positive sequence

T
=
(

t
k

)

k
=
1

∞

T=(t_k)_{k=1}^\infty

tending to zero and such that
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="sup Underscript k element-of double-struck upper N Endscripts StartFraction upper M left-parenthesis c t Subscript k Baseline right-parenthesis Over upper M left-parenthesis t Subscript k Baseline right-parenthesis EndFraction greater-than normal infinity comma for all c greater-than 1 comma">

sup

k
∈

N

M
(
c

t
k

)

M
(

t
k

)

>
∞
,
 for all 
c
>
1
,

\begin{equation*} \sup _{k\in \mathbb {N}}\frac {M(ct_k)}{M(t_k)} >\infty ,\text { for all }c>1, \end{equation*}

that is,

M
M

satisfies the

Δ
2

\Delta _2

condition with respect to

T
T

.

Consequently, we show that for each Orlicz function with lower Boyd index

α
M

>
∞

\alpha _M > \infty

there exists an Orlicz function

N
N

such that:

(a) there exists a positive sequence

T
=
(

t
k

)

k
=
1

∞

T=(t_k)_{k=1}^\infty

tending to zero such that

N
N

satisfies the

Δ
2

\Delta _2

condition with respect to

T
T

, and

(b) the space

h
N

h_N

is isomorphic to a subspace of

h
M

h_M

generated by one vector.

We apply this result to find the maximal possible order of Gâteaux differentiability of a continuous bump function on the Orlicz space

h
M

(
Γ
)

h_M(\Gamma )

for

Γ
\Gamma

uncountable.
The State of Use and Utility of Negative Controls in Pharmacoepidemiologic Studies
Authors: Zafari Zafar , Park Jeong-eun , Shah Chintal H , dosReis Susan , Gorman Emily F , Hua Wei , Ma Yong , Tian Fang
Published: October 2023

Uses of real-world data in drug safety and effectiveness studies are often challenged by various sources of bias. We undertook a systematic search of the published literature through September 2020 to evaluate the state of use and utility of negative controls to address bias in pharmacoepidemiologic studies. Two reviewers independently evaluated study eligibility and abstracted data. Our search identified 184 eligible studies for inclusion. Cohort studies (115, 63%) and administrative data (114, 62%) were, respectively, the most common study design and data type used. Most studies used negative control outcomes (91, 50%), and for most studies the target source of bias was unmeasured confounding (93, 51%). We identified 4 utility domains of negative controls: 1) bias detection (149, 81%), 2) bias correction (16, 9%), 3) P-value calibration (8, 4%), and 4) performance assessment of different methods used in drug safety studies (31, 17%). The most popular methodologies used were the 95% confidence interval and P-value calibration. In addition, we identified 2 reference sets with structured steps to check the causality assumption of the negative control. While negative controls are powerful tools in bias detection, we found many studies lacked checking the underlying assumptions.

This article is part of a Special Collection on Pharmacoepidemiology.
Effect of daily ingestion of Bifidobacterium and dietary fiber on vascular endothelial function: a randomized, double-blind, placebo-controlled, parallel-group comparison study
Authors: Azuma Naoki , Saito Yasuo , Nishijima Tomohiko , Aoki Ryo , Nishihira Jun
Published: October 2023

Bifidobacterium animalis subsp. lactis GCL2505 (GCL2505) improves the intestinal microbiota and reduces human visceral fat. This randomized, double-blind, placebo-controlled, parallel-group study was conducted to examine the effects of inulin, a prebiotic dietary fiber, and GCL2505 on vascular endothelial function in healthy subjects (n = 60). The test drink contained 2.0 g/100 g inulin and 1.0 × 1010 colony-forming units/100 g GCL2505 and was consumed daily for 12 weeks. Flow-mediated dilation was set as the primary endpoint. Subgroup analysis of vascular endothelial function demonstrated a significant increase in the change of flow-mediated dilation (%) from weeks 0 to 12 in the GCL2505 and inulin group (n = 24) compared with the placebo group (n = 23), while an improving trend in low-density lipoprotein cholesterol and plasminogen activator inhibitor-1 were confirmed. Our results indicated that the test drink had a positive effect on vascular endothelial function and related blood parameters.
Layer 1 of somatosensory cortex: an important site for input to a tiny cortical compartment
Authors: Ledderose Julia M T , Zolnik Timothy A , Toumazou Maria , Trimbuch Thorsten , Rosenmund Christian , Eickholt Britta J , Jaeger Dieter , Larkum Matthew E , Sachdev Robert N S
Published: October 2023

Neocortical layer 1 has been proposed to be at the center for top-down and bottom-up integration. It is a locus for interactions between long-range inputs, layer 1 interneurons, and apical tuft dendrites of pyramidal neurons. While input to layer 1 has been studied intensively, the level and effect of input to this layer has still not been completely characterized. Here we examined the input to layer 1 of mouse somatosensory cortex with retrograde tracing and optogenetics. Our assays reveal that local input to layer 1 is predominantly from layers 2/3 and 5 pyramidal neurons and interneurons, and that subtypes of local layers 5 and 6b neurons project to layer 1 with different probabilities. Long-range input from sensory-motor cortices to layer 1 of somatosensory cortex arose predominantly from layers 2/3 neurons. Our optogenetic experiments showed that intra-telencephalic layer 5 pyramidal neurons drive layer 1 interneurons but have no effect locally on layer 5 apical tuft dendrites. Dual retrograde tracing revealed that a fraction of local and long-range neurons was both presynaptic to layer 5 neurons and projected to layer 1. Our work highlights the prominent role of local inputs to layer 1 and shows the potential for complex interactions between long-range and local inputs, which are both in position to modify the output of somatosensory cortex.
Brain asymmetry is globally different in males and females: exploring cortical volume, area, thickness, and mean curvature
Authors: Dumitru Magda L
Published: October 2023

Brain asymmetry is a cornerstone in the development of higher-level cognition, but it is unclear whether and how it differs in males and females. Asymmetry has been investigated using the laterality index, which compares homologous regions as pairwise weighted differences between the left and the right hemisphere. However, if asymmetry differences between males and females are global instead of pairwise, involving proportions between multiple brain areas, novel methodological tools are needed to evaluate them. Here, we used the Amsterdam Open MRI collection to investigate sexual dimorphism in brain asymmetry by comparing laterality index with the distance index, which is a global measure of differences within and across hemispheres, and with the subtraction index, which compares pairwise raw values in the left and right hemisphere. Machine learning models, robustness tests, and group analyses of cortical volume, area, thickness, and mean curvature revealed that, of the three indices, distance index was the most successful biomarker of sexual dimorphism. These findings suggest that left–right asymmetry in males and females involves global coherence rather than pairwise contrasts. Further studies are needed to investigate the biological basis of local and global asymmetry based on growth patterns under genetic, hormonal, and environmental factors.
Does Kono-S Anastomosis Reduce Recurrence in Crohn’s Disease Compared with Conventional Ileocolonic Anastomosis? A Nationwide Propensity Score-matched Study from GETAID Chirurgie Group [KoCoRICCO Study]
Authors: Alibert Line , Betton Louis , Falcoz Antoine , Manceau Gilles , Benoist Stéphane , Zerbib Philippe , Podevin Juliette , Maggiori Léon , Brouquet Antoine , Tyrode Gaëlle , Vuitton Lucine , Vernerey Dewi , Lefevre Jérémie H , Lakkis Zaher
Published: October 2023

Background and Aims

Postoperative recurrence is a major concern in Crohn’s disease. The Kono-S anastomosis has been described to reduce the rate of recurrence. However, the level of evidence for its effectiveness remains low. The KoCoRICCO study aimed to compare outcomes between Kono-S anastomosis and conventional anastomosis in two nationwide, prospective cohorts.

Methods

Adult patients with Crohn’s disease, who underwent ileocolonic resection with Kono-S anastomosis, were prospectively included in seven referral centres between 2020 and 2022. Patients with conventional side-to-side anastomosis were enrolled from a previously published cohort. A propensity score analysis was performed to compare recurrence at first endoscopy in a matched 1:2 ratio population.

Results

A total of 433 patients with ileocolonic anastomosis were enrolled, of whom 155 had a Kono-S anastomosis. Before matching, both groups were unbalanced for preoperative, intraoperative, and postoperative characteristics. After matching patients with available endoscopic follow-up, endoscopic recurrence ≥i2 was found in 47.5% of the Kono-S group and 44.3% of the conventional side-to-side group [p = 0.6745].

Conclusions

The KoCoRICCO study suggests that Kono-S anastomosis does not reduce the risk of endoscopic recurrence in Crohn’s disease compared with conventional side-to-side anastomosis. Further research with a longer follow-up is necessary to determine whether there is a potential benefit on surgical recurrence.
Lymphoma in Patients with Inflammatory Bowel Disease: A Multicentre Collaborative Study Between GETAID and LYSA
Authors: Muller Marie , Broséus Julien , Guilloteau Adrien , Wasse Stéphane , Thiéblemont Catherine , Nancey Stéphane , Cadiot Guillaume , Amiot Aurélien , Laharie David , Vieujean Sophie , Bouhnik Yoram , Martineau Chloé , Michiels Christophe , Hebuterne Xavier , Savoye Guillaume , Franchimont Denis , Seksik Philippe , Beaugerie Laurent , Maynadié Marc , Feugier Pierre , Peyrin-Biroulet Laurent
Published: October 2023

Background

Inflammatory bowel disease [IBD] is associated with an increased risk of developing lymphoma. Although recent data have clarified the epidemiology of lymphoma in IBD patients, the clinical and pathological characteristics of lymphoma in IBD remain poorly known.

Methods

Patients with IBD and lymphoma were retrospectively identified in the framework of a national collaborative study including the Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif [GETAID] and the Lymphoma Study Association [LYSA]. We characterized clinical and prognostic features for the three most frequent lymphoma subtypes occurring in IBD. We performed a multicentre case-control study. Controls [lymphoma de novo] were matched [5:1] to cases on gender, age at diagnosis, lymphoma subtype, year of diagnosis, and IPI/FLIPI indexes. Overall survival and progression-free survival were compared between cases and controls.

Results

In total, 133 IBD patients with lymphoma were included [males = 62.4%, median age at lymphoma diagnosis = 49 years in males; 42 years in females]. Most had Crohn’s disease [73.7%] and were exposed to thiopurines [59.4%]. The most frequent lymphoma subtypes were diffuse large B cell lymphoma [DLBCL, 45.1%], Hodgkin lymphoma [HL, 18.8%], and follicular lymphoma [FL, 10.5%]. When matched with 365 controls, prognosis was improved in IBD patients with DLBCL compared to controls [p = 0.0064, hazard ratio = 0.36] or similar [HL and FL].

Conclusions

Lymphomas occurring in IBD patients do not seem to have a worse outcome than in patients without IBD. Due to the rarity of this situation, such patients should be managed in expert centres.
Numerical exploration of factors that control stress amplification in Earth's lithosphere
Authors: Feng He , Gerbi Christopher C , Johnson Scott E
Published: October 2023

The mechanical heterogeneity of Earth's lithosphere leads to significant amplification of stresses across spatial scales ranging from mineral grains to tectonic plates. These stress amplifications play a key role in mechanical and chemical processes within the rock that affect bulk rock strength. Identifying the most effective causes of stress amplification is critical for understanding processes such as strain localization and fluid transport at scales ranging from microshear zones to tectonic plate boundaries. However, studies quantifying and predicting stress heterogeneities and amplifications are limited. We used numerical modelling of two-phase isotropic viscous systems to explore the factors influencing and controlling stress amplification and the potential magnitude of stress amplification in viscous regimes. We found the most geologically relevant amplification factors to be weak-phase spacing, rheological contrast and loading type. Our results indicate that stress amplification can reach a factor of ∼9 under specific conditions, but most of our experiments suggest amplifications at or below a factor of 2. Pressure differences across the model domains generally do not exceed ∼55 MPa, but some are as high as ∼110 MPa. The stress and pressure amplifications resulting from our analyses are large enough to drive a variety of geologically important processes such as failure and strain localization, as well as transient permeability and fluid migration.
Fatal drowning in Indonesia: understanding knowledge gaps through a scoping review
Authors: Cenderadewi Muthia , Devine Susan G , Sari Dian Puspita , Franklin Richard C
Published: October 2023

Little is known about unintentional drowning deaths in Indonesia, the world’s fourth most populous and largest archipelagic country. This study aimed to describe the epidemiology and risk factors of unintentional drowning in Indonesia and explore existing health promotion and drowning prevention approaches in Indonesia within a socio-ecological health promotion framework. A scoping review, guided by PRISMA-ScR, was conducted to locate peer-reviewed studies and government reports/policy documents published until May 2023, in English or Indonesian language, using MEDLINE (Ovid), CINAHL, Informit, PsycINFO (ProQuest), Scopus, SafetyLit, BioMed Central and Google Scholar, Indonesian journal databases (Sinta, Garuda) and government agencies websites around the terms: drown, swim, flood, hurricane, cyclone, disaster, water rescue and maritime/boat safety. This review identified 32 papers. However, a paucity of information on unintentional drowning rates, risk factors and prevention in Indonesia was noted. The unavailability of a coordinated national drowning data collection system in Indonesia, from which national and subnational subcategory data can be collected, underlines the possibility of under-representation of drowning mortality. The association between various exposures and drowning incidents has not been fully investigated. An over-reliance on individual-focused, behaviour-based, preventive measures was observed. These findings highlight the need for improving drowning surveillance to ensure the availability and reliability of drowning data; and strengthening research to understand the risk factors for drowning and delivery of drowning prevention programs. Further policy development and research focusing on health promotion approaches that reflect a socio-ecological approach to drowning prevention in Indonesia is imperative.
Prototype Pathogens for Vaccine and Monoclonal Antibody Countermeasure Development: NIAID Workshop Process and Outcomes for Viral Families of Pandemic Potential
Authors: Deschamps Anne M , DeRocco Amanda J , Bok Karin , Patterson L Jean
Published: October 2023

Given the increased risk of pandemics driven by emerging and reemerging infectious diseases, it is imperative that the United States and global scientific community be better prepared for future threats by prioritizing and launching key research programs and strategies. In December 2021, the National Institute of Allergy and Infectious Diseases (NIAID) published its pandemic preparedness plan, which focuses on the prototype pathogen approach for medical countermeasure development. The plan was introduced before its release at a NIAID-hosted workshop in November 2021 that featured scientific experts from the extramural community, government, and the private sector and focused on selection of prototype pathogens from 10 viral families with pandemic risk and moderate resources. This article will serve as an introduction to this special issue and will briefly define the prototype pathogen approach, describe the workshop goals and process for outcomes, and provide an outline of the viral working group articles to follow and future directions for NIAID.
Paramyxoviruses: Pathogenesis, Vaccines, Antivirals, and Prototypes for Pandemic Preparedness
Authors: Duprex W Paul , Dutch Rebecca Ellis
Published: October 2023

The Paramyxoviridae family includes established human pathogens such as measles virus, mumps virus, and the human parainfluenza viruses; highly lethal zoonotic pathogens such as Nipah virus; and a number of recently identified agents, such as Sosuga virus, which remain poorly understood. The high human-to-human transmission rate of paramyxoviruses such as measles virus, high case fatality rate associated with other family members such as Nipah virus, and the existence of poorly characterized zoonotic pathogens raise concern that known and unknown paramyxoviruses have significant pandemic potential. In this review, the general life cycle, taxonomic relationships, and viral pathogenesis are described for paramyxoviruses that cause both systemic and respiratory system–restricted infections. Next, key gaps in critical areas are presented, following detailed conversations with subject matter experts and based on the current literature. Finally, we present an assessment of potential prototype pathogen candidates that could be used as models to study this important virus family, including assessment of the strengths and weaknesses of each potential prototype.
Protection for Hire: Cooperation through Regional Organizations
Authors: Cottiero Christina
Published: October 2023

There is growing evidence that leaders cooperate through regional intergovernmental organizations (RIOs) to address domestic security challenges. What sustains this collaboration? I present a theory of regional cooperation driven by mutual interest in stability and protection for heads of state. RIOs support the development of rules and norms around contributing to regional security and can legitimize pro-government military interventions. Leaders concerned that they may need external support—particularly against members of their own military—cooperate to remain in good standing with co-members. Using original security personnel deployment data for members of four Africa-based RIOs with mutual defense pacts between 1990 and 2017, I show that leaders facing higher coup risk were more likely to deploy personnel to support co-members. I also find evidence for the underlying mechanism—that these leaders contribute because they expect RIO members to reciprocate support in the future. Leaders who contributed more personnel to support co-members, and leaders who contributed more often, were more likely to receive military support from co-members in the future. These findings shed light on the dynamics sustaining regional security cooperation.
Differential sensitivity of climate conditions on birth weight genetic values in mice divergently selected for birth weight residual variance
Authors: El-Ouazizi El-Kahia Laila , Formoso-Rafferty Nora , Cervantes Isabel , Gutiérrez Juan Pablo
Published: October 2023

After 32 generations of a divergent selection experiment for residual variance of birth weight in mice, two divergent lines were thus obtained: the heterogeneous line (H-line) and the homogeneous line (L-line). Throughout the generations, differences were observed between the two lines in traits such as litter size, survival at weaning, and birth weight variability caused by unidentified environmental conditions. The L-line exhibited advantages in terms of higher survival rates, larger litter sizes, and less sensitivity to changes in food intake. The study is an examination of the effects of climate as an environmental factor on the performance of these animals. Climate factors including maximum, minimum, and mean temperature (T), humidity (H), and TH index; at three stages (the fecundation, a week before the parturition and the parturition), were linked to a birth weight dataset consisting of 22,614 records distributed as follows: 8,853 corresponding to the H-line, 12,649 to the L-line, and 1,112 to the initial population. Out of the 27 analyzed climatic variables, the maximum temperature 1 wk before parturition (MXTW) was identified as the most influential when comparing heteroscedastic models with the deviance information criterion. The order of Legendre polynomial to apply in the following random regression model was tested by a cross-validation using homoscedastic models. Finally, MXTW was compared on how it affected the two divergent lines by analyzing predicted breeding values (PBV) obtained from a random regression heteroscedastic model. The mean PBV of the H-line in the first generation showed a range of 0.070 g with a negative slope, which was 35 times higher than the range obtained for the L-line, which varied within 0.002 g. In the last generation of selection, the H-line exhibited greater instability of PBV across temperatures, with a difference of 0.101 g between the maximum and minimum mean PBV, compared to 0.017 g for the L-line. The standard deviations of the slopes in the H-line were more dispersed than in the L-line. Unlike the H-line, the L-line had slopes that were not significantly different from 0 throughout the generations of selection, indicating greater stability in response to MXTW variations. The H-line exhibited a higher sensitivity to changes in MXTW, particularly in birth weight, with the L-line being more stable. The selection for uniformity of birth weight could lead to less sensitive animals under environmental changes.
Do adult Magicicada (Hemiptera: Cicadidae) feed? Historical perspectives and evidence from molecular gut content analysis
Authors: Hepler James R , Cooper W Rodney , Cullum John P , Dardick Chris , Dardick Liam , Nixon Laura J , Pouchnik Derek J , Raupp Michael J , Shrewsbury Paula , Leskey Tracy C
Published: October 2023

The periodical cicadas in the genus Magicicada are remarkable for their unusual life histories and dramatic synchronized emergences every 13 or 17 years. While aspects of their evolution, mating behaviors, and general biology have been well-characterized, there is surprising uncertainty surrounding the feeding habits of the short-lived adult stage. Despite a tentative scientific consensus to the contrary, the perception that adult Magicicada do not feed has persisted among the general public, and recent studies are lacking. We directly investigated the feeding behavior of Magicicada spp. through high-throughput sequencing (HTS)-based dietary analysis of nymphs, freshly molted (teneral) adults, and fully sclerotized adults collected from orchard and wooded habitats during the 2021 emergence of Brood X. Identifiable plant DNA (trnF, ITS amplicons) was successfully recovered from nymphs and adults. No plant DNA was recovered from teneral adults, suggesting that all DNA recovered from sclerotized adults was ingested during the post-teneral adult stage. Both nymphs and adults were found to have ingested a range of woody and herbaceous plants across 17 genera and 14 families. Significantly more plant genera per individual were recovered from adults than from nymphs, likely reflecting the greater mobility of the adult stage. We hypothesize that the demonstrated ingestion of plant sap by Magicicada adults is driven by a need to replace lost water and support specialized bacteriome-dwelling endosymbionts that cicadas depend upon for growth and development, which constitutes true feeding behavior.
Clinical impact of sarcopenia for overweight or obese patients with colorectal cancer
Authors: Chen Wei-Zhe , Lin Feng , Yu Ding-Ye , Ren Qi , Zhang Feng-Min , Shen Zi-Le , Chen Wen-Hao , Dong Qian-Tong , Yu Zhen
Published: October 2023

Background

Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer.

Methods

We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis.

Results

Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications.

Conclusions

Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients.
Human papillomavirus–associated anal squamous cell carcinoma: sociodemographic, geographic, and county-level economic trends in incidence rates—United States, 2001-2019
Authors: Gopalani Sameer Vali , Senkomago Virginia , Rim Sun Hee , Saraiya Mona
Published: October 2023

Background

Incidence of anal squamous cell carcinoma is increasing, but vaccination against human papillomavirus (HPV) and removal of precancerous anal lesions could prevent new cases. The overall HPV-associated cancer incidence is reported to be higher in rural populations and in counties with lower economic status. We assessed these differences specifically for HPV-associated anal squamous cell carcinoma and described the geographic, county-level economic, and sociodemographic variations in incidence rates and trends.

Methods

We analyzed data from the US Cancer Statistics to assess age-standardized incidence rates of HPV-associated squamous cell carcinomas among adults aged 18 years and older from 2001 to 2019. We calculated rate ratios and 95% confidence intervals to examine differences in incidence rates. We also quantified changes in incidence rates over time using joinpoint regression.

Results

From 2001 to 2019, 72 421 new cases of HPV-associated anal squamous cell carcinoma were diagnosed among women (2.8 per 100 000) and 37 147 among men (1.7 per 100 000). Age-standardized incidence rates were higher in the South compared with other census regions and in counties ranked in the bottom 25% and 25%-75% economically than in the top 25%. The overall incidence rate increased in women but remained stable in men during 2009-2019. Incidence rates increased in adults aged 50 years and older but decreased among those aged 40-44 years from 2001 to 2019 in women and from 2007 to 2019 in men.

Conclusions

There were inequities in HPV-associated anal squamous cell carcinoma incidence by geographic and county-level economic characteristics. Failure to improve vaccine and treatment equity may widen existing disparities.
Cost of Medically Attended RSV Among Medicaid Beneficiaries ≤2 Years of Age by Underlying Risk Condition
Authors: Choi Yoonyoung , Finelli Lynn
Published: October 2023

We evaluated costs for respiratory syncytial virus (RSV) medical attention in children aged <24 months using MarketScan® Medicaid Multi-State claims database 2015–2019. Average cost was highest for RSV hospitalization with intensive care unit (ICU) admission ($23 514–24 835), followed by no ICU admission ($8039–8990), ED visits ($463–482), and outpatient visits ($145–151). Cost was higher for those with comorbidities.
Patient Registry of Upper Limb Outcomes (PRULO): a protocol for an orthopaedic clinical quality registry to monitor treatment outcomes
Authors: Scholes Corey , Eng Kevin , Harrison-Brown Meredith , Ebrahimi Milad , Brown Graeme , Gill Stephen , Page Richard
Published: October 2023

Registries have been widely utilized to track clinical results in observational cohorts for quality improvement. They are successful in orthopaedics, particularly in the context of arthroplasties where they have optimized implant selection, improved patient safety and identified underperforming implants. However, equivalent systems to monitor outcomes in soft-tissue disorders are lacking. This protocol described the design, ethics and implementation of a regional registry focusing on upper limb soft tissue orthopaedic conditions. Patient Registry of Upper Limb pathology Outcomes (PRULO) is a multi-cohort, prospective observational, clinical quality registry collating clinical data and patient-reported outcomes for patients presenting to a specialist orthopaedic clinic with upper limb pathology. PRULO is currently a single-centre study involving three clinician investigators, which aims to determine what patient characteristics, pathology factors and treatment strategies are associated with treatment success within 2 years of surgical or non-surgical treatment of pathology. PRULO captures patient-reported outcomes (VAS, EQ5D-5 L, QuickDASH, MODEMS-Expectations and Satisfaction, WORC, WOSI), clinical and radiological data. Data points are recorded at practice registration, after initial consultation, intraoperatively and at 3, 6, 12 and 24 months. Inclusion criteria are patients aged 16 and above offered treatment by the surgeons for upper limb orthopaedic pathology. Patient cohorts will include shoulder conditions affecting the rotator cuff (tear, tendinopathy), conditions associated with glenohumeral instability, as well as all other conditions presenting in the shoulder elbow, hand and wrist, according to the surgeon-generated diagnosis. Ethical approval was obtained by the Barwon Health Research Ethics Committee (19/70).
Optical Measurement of the Stoichiometry of Thin-Film Compounds Synthetized From Multilayers: Example of Cu(In,Ga)Se2
Authors: Poeira Ricardo G , Siopa Daniel , Anacleto Pedro , Sadewasser Sascha , Dale Phillip J
Published: October 2023

The properties of centimeter-sized thin-film compound semiconductors depend upon the morphology and chemical composition of the multiple submicrometer-thick elemental and alloy precursor layers from which they are synthesized. The challenge is to characterize the individual precursor layers over these length scales during a multistep synthesis without altering or contaminating them. Conventional electron and X-ray-based morphological and compositional techniques are invasive, require preparation, and are thus incompatible with in-line synthesis processes. In a proof-of-concept study, we applied confocal laser scanning microscopy (CLSM) as a noninvasive optical imaging technique, which measures three-dimensional surface profiles with nanoscale resolution, to this challenge. Using an array of microdots containing Cu(In,Ga)Se2 semiconductor layers for solar cells as an example, we performed CLSM correlative studies to quantify morphological and layer thickness changes during four stages of a thin-film compound synthesis. Using simple assumptions, we measured the micrometer-scale spatially resolved chemical composition of stacked precursor layers to predict the final material phases formed and predict relative device performance. The high spatial resolution, coupled with the ability to measure sizeable areas without influencing the synthesis at high speed, makes CLSM an excellent prospect for research and quality control tool for thin films.
Solaris photometric survey: Search for circumbinary companions using eclipse timing variations
Authors: Moharana A , Hełminiak K G , Marcadon F , Pawar T , Pawar G , Garczyński P , Perła J , Kozłowski S K , Sybilski P , Ratajczak M , Konacki M
Published: October 2023

Eclipse timing variations (ETVs) have been a successful tool for detecting circumbinary companions to eclipsing binaries (EBs). While TESS and Kepler have been prolific for ETV searches, they sometimes can be limited by time and sky coverage, a limitation that can be addressed by specialized ground-based ETV surveys. We present the initial results from the Solaris photometric survey, which uses four 0.5-m robotic telescopes in the Southern hemisphere to look for circumbinary companions. We present the method of light-curve extraction, detrending, and EB modelling using observations from the Solaris network. Using these light curves, we extract precise eclipse timings for seven EBs and look for companions using a Lomb–Scargle periodogram search. We find two possible periodic signals for the target GSC 08814–01026. With the system having strong activity, we check for the feasibility of orbital solutions at these two periods. We find that the 245 ± 1 d period is due to an M dwarf-mass companion. This makes GSC 08814–01026 a candidate compact hierarchical triple system. The other periodic signal at 146 ± 1 d is an artefact of stellar activity.
Seeding the CGM: how satellites populate the cold phase of milky way haloes
Authors: Roy Manami , Su Kung-Yi , Tonnesen Stephanie , Fielding Drummond B , Faucher-Giguère Claude-André
Published: October 2023

The origin of the cold phase in the circumgalactic medium (CGM) is a highly debated question. We investigate the contribution of satellite galaxies to the cold gas budget in the CGM of a Milky Way-like host galaxy. We perform controlled experiments with three different satellite mass distributions and identify several mechanisms by which satellites can add cold gas to the CGM, including ram pressure stripping and induced cooling in the mixing layer of the stripped cold gas. These two mechanisms contribute a comparable amount of cold gas to the host CGM. We find that the less massive satellites (≤109M⊙) not only lose all of their cold gas in a short period (∼ 0.5–1 Gyr), but their stripped cold clouds also mix with the hot CGM gas and get heated up quickly. However, stellar feedback from these less massive satellites can hugely alter the fate of their stripped gas. Feedback speeds up the destruction of the stripped cold clouds from these satellites by making them more diffuse with more surface area. On the other hand, the more massive satellites (LMC or SMC-like ∼1010M⊙) can add cold gas to the total gas budget of the host CGM for several Gyr.
A halo model for cosmological Lyman-limit systems
Authors: Theuns Tom , Chan T K
Published: October 2023

We present an analytical model for cosmological Lyman-limit systems (lls) that successfully reproduces the observed evolution of the mean free path (λeff) of ionizing photons. The evolution of the co-moving mean free path is predominantly a consequence of the changing meta galactic photoionization rate and the increase with cosmic time of the minimum mass below which haloes lose their gas due to photoheating. In the model, Lyman-limit absorption is caused by highly ionized gas in the outskirt of dark matter haloes. We exploit the association with haloes to compute statistical properties of λeff and of the bias, b, of lls. The latter increases from b ∼ 1.5 → 2.6 from redshifts z = 2 → 6. Combined with the rapid increase with redshift of the bias of the haloes that host a quasar, the model predicts a rapid drop in the value of λeff when measured in quasar spectra from z = 5 → 6, whereas the actual value of λeff falls more smoothly. We derive an expression for the effective optical depth due to Lyman limit absorption as a function of wavelength and show that it depends sensitively on the poorly constrained number density of lls as a function of column density. The optical depth drops below unity for all wavelengths below a redshift of ∼2.5 which is therefore the epoch when the Universe first became transparent to ionizing photons.
Tides in clouds: control of star formation by long-range gravitational force
Authors: Li Guang-Xing
Published: October 2023

Gravity drives the collapse of molecular clouds through which stars form, yet the exact role of gravity in cloud collapse remains a complex issue. Studies point to a picture where star formation occurs in clusters. In a typical, pc-sized cluster-forming region, the collapse is hierarchical, and the stars should be born from regions of even smaller sizes (${\approx} 0.1\,\rm pc$). The origin of this spatial arrangement remains under investigation. Based on a high-quality surface density map towards the Perseus region, we construct a 3D density structure, compute the gravitational potential, and derive eigenvalues of the tidal tensor (λmin, λmid, λmax, λmin < λmid < λmax), analyse the behaviour of gravity at every location, and reveal its multiple roles in cloud evolution. We find that fragmentation is limited to several isolated, high-density ‘islands’. Surrounding them, is a vast amount of the gas ($75~{{ \rm per\ cent}}$ of the mass, $95~{{ \rm per\ cent}}$ of the volume) that stays under the influence of extensive tides where fragmentation is suppressed. This gas will be transported towards these regions to fuel star formation. The spatial arrangement of regions under different tides explains the hierarchical and localized pattern of star formation inferred from the observations. Tides were first recognized by Newton, yet this is the first time its dominance in cloud evolution has been revealed. We expect this link between cloud density structure and role gravity to be strengthened by future studies, resulting in a clear view of the star formation process.
Insights into RAG Evolution from the Identification of “Missing Link” Family A RAGL Transposons
Authors: Martin Eliza C , Le Targa Lorlane , Tsakou-Ngouafo Louis , Fan Tzu-Pei , Lin Che-Yi , Xiao Jianxiong , Huang Ziwen , Yuan Shaochun , Xu Anlong , Su Yi-Hsien , Petrescu Andrei-Jose , Pontarotti Pierre , Schatz David G
Published: October 2023

A series of “molecular domestication” events are thought to have converted an invertebrate RAG-like (RAGL) transposase into the RAG1–RAG2 (RAG) recombinase, a critical enzyme for adaptive immunity in jawed vertebrates. The timing and order of these events are not well understood, in part because of a dearth of information regarding the invertebrate RAGL-A transposon family. In contrast to the abundant and divergent RAGL-B transposon family, RAGL-A most closely resembles RAG and is represented by a single orphan RAG1-like (RAG1L) gene in the genome of the hemichordate Ptychodera flava (PflRAG1L-A). Here, we provide evidence for the existence of complete RAGL-A transposons in the genomes of P. flava and several echinoderms. The predicted RAG1L-A and RAG2L-A proteins encoded by these transposons intermingle sequence features of jawed vertebrate RAG and RAGL-B transposases, leading to a prediction of DNA binding, catalytic, and transposition activities that are a hybrid of RAG and RAGL-B. Similarly, the terminal inverted repeats (TIRs) of the RAGL-A transposons combine features of both RAGL-B transposon TIRs and RAG recombination signal sequences. Unlike all previously described RAG2L proteins, RAG2L-A proteins contain an acidic hinge region, which we demonstrate is capable of efficiently inhibiting RAG-mediated transposition. Our findings provide evidence for a critical intermediate in RAG evolution and argue that certain adaptations thought to be specific to jawed vertebrates (e.g. the RAG2 acidic hinge) actually arose in invertebrates, thereby focusing attention on other adaptations as the pivotal steps in the completion of RAG domestication in jawed vertebrates.
MethMotif.Org 2024: a database integrating context-specific transcription factor-binding motifs with DNA methylation patterns
Authors: Dyer Matthew , Lin Quy Xiao Xuan , Shapoval Sofiia , Thieffry Denis , Benoukraf Touati
Published: October 2023

MethMotif (https://methmotif.org) is a publicly available database that provides a comprehensive repository of transcription factor (TF)-binding profiles, enriched with DNA methylation patterns. In this release, we have enhanced the platform, expanding our initial collection to over 700 position weight matrices (PWM), all of which include DNA methylation profiles. One of the key advancements in this release is the segregation of TF-binding motifs based on their cofactors and DNA methylation status. We have previously demonstrated that gene ontology (GO) enriched terms associated with TF target genes may differ based on their association with alternative cofactors and DNA methylation status. MethMotif provides precomputed GO annotations for each human TF of interest, as well as for TF-co-TF complexes, enabling a comprehensive analysis of TF functions in the context of their co-factors. Additionally, MethMotif has been updated to encompass data for two new species, Mus musculus and Arabidopsis thaliana, widening its applicability to a broader community. MethMotif stands out as the first and only TF-binding motifs database to incorporate context-specific PWM coupled with epigenetic information, thereby enlightening context-specific TF functions. This enhancement allows the community to explore and gain deeper insights into the regulatory mechanisms governing transcriptional processes.
Supplemental organic trace minerals and a yeast culture product in newly weaned steers: effects of use and delivery method on growth performance and hepatic trace mineral content
Authors: Ribeiro Thiago Lauro Maia , Francis Forest L , Gubbels Erin R , Griffin Jason E , Rusche Warren C , Smith Zachary K
Published: October 2023

The objective of this study was to determine if supplementation and delivery method of a “stress pack” composed of organic trace minerals and Saccharomyces cerevisiae yeast culture product influenced growth performance, feed efficiency, and hepatic trace mineral concentration in newly weaned steers. Crossbred steers (n = 192; 256 ± 14.0 kg) were used in a 49-day receiving phase experiment. Within 36 hours of weaning, steers were weighed, allotted to 24 pens (n = 8 steers/pen; 8 pens/treatment), and randomly assigned to treatments: 1) a traditional receiving diet (CON), 2) a traditional receiving diet plus the “stress-pack” directly in the diet (FORCE), and 3) a traditional receiving diet plus a low-moisture, cooked molasses block fortified with the “stress-pack” (TUB). The “stress-pack” was offered the first 28 day of the 49-day receiving period. Due to adverse weather conditions forecasted on day 1, biopsy samples were collected from a subsample of steers (n = 14 steers) on day 1 to establish hepatic trace mineral concentration baseline. Steers were selected based on the mean body weight (BW) from allotment (day −1) of the pen for collection of subsequent samples (n = 1 steer/pen) on days 14, 28, and 49 for hepatic trace mineral concentration determination. Cumulative dry matter intake (DMI) (P = 0.01) was greater for FORCE compared to CON and TUB. Final BW and average daily gain (ADG) tended (P ≤ 0.10) to be greater for FORCE compared to TUB and CON by 5.4% and 9.4%, respectively. Feed efficiency did not differ between treatments (P = 0.28). A treatment × day interaction (P ≤ 0.01) for hepatic Cu concentration was noted. The FORCE treatment had greater hepatic Cu compared to TUB and CON for the entire period. The steers that received TUB had greater hepatic Cu compared to CON on days 14 and 28, but similar to CON on day 49. The addition of a “stress-pack” to diets offered to newly weaned cattle enhanced hepatic trace mineral concentration, and delivery method influences DMI and daily gain.
The spectrum of central nervous system manifestations in leprosy: a systematic review of published case reports and case series
Authors: Garg Ravindra Kumar , Uniyal Ravi , Pandey Shweta , Tejan Nidhi , Rizvi Imran , Sharma Praveen Kumar , Kumar Neeraj , Malhotra Hardeep Singh
Published: October 2023

Background

This systematic review aimed to investigate central nervous system (CNS) involvement in leprosy by analysing multiple cohort studies, individual cases and case series.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. PubMed, Scopus and Embase databases were searched up to 8 July 2023, using a predefined search strategy. Inclusion criteria included patients diagnosed with leprosy with evidence of CNS involvement. The quality of the included cases was evaluated using the Joanna Briggs Institute checklist.

Results

A total of 34 records were identified, including 18 cohort studies and 16 reports describing 27 isolated cases. Autopsies revealed macroscopic changes in the spinal cord, neurofibrillary tangles and senile plaques. Mycobacterium leprae was detected in neurons of the medulla oblongata and spinal cord using PCR and phenolic glycolipid 1 staining. Cerebrospinal fluid (CSF) analysis showed inflammatory changes, increased gamma globulins and detection of Mycobacterium leprae antigens and antibodies. In 21 patients (78%), spinal cord/brachial plexus abnormities were detected. In the majority, MRI revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity in the cervical cord. In patients with brainstem involvement, T2/FLAIR hyperintensity was noted in the cerebellar peduncles, facial nerve nuclei and/or other cranial nerve nuclei. Brain parenchymal involvement was noted in three patients.

Conclusions

This systematic review provides evidence of CNS involvement in leprosy, based on autopsy findings, neuroimaging, CSF analysis and neurophysiological studies.
Precipitated Opioid Withdrawal Treated With Ketamine in a Hospitalized Patient: A Case Report
Authors: Christian Nicholaus J. , Butner Jenna L. , Evarts Mariah S. , Weimer Melissa B.
Published: October 2023

Background

Although initiating buprenorphine in the presence of full opioid agonists has always been a clinical dilemma, the transition to primarily fentanyl in the drug supply has increased the urgency to find appropriate treatments for precipitated opioid withdrawal (POW). Although rare, lack of evidence on how to best treat POW threatens clinician and patient comfort in initiating life-saving medication for opioid use disorder. Ketamine has been used in emergency department settings to treat POW; this is the first case report of ketamine use in a hospitalized patient.

Case Summary

A 38-year-old male patient with severe opioid use disorder presented to the emergency department with suicidality and opioid withdrawal 24 hours after last fentanyl use. In the first 24 hours of admission, he received sublingual buprenorphine-naloxone (BNX) 16–4 mg, resulting in Clinical Opiate Withdrawal Scale score increasing from 13 to over 36. The patient was admitted, and addiction medicine was consulted. The patient was diagnosed with POW, started on ketamine infusion, and given additional BNX 8–2 mg. Twelve hours after the ketamine infusion, the patient’s Clinical Opiate Withdrawal Scale score improved to 18 but remained elevated. He received a second ketamine infusion plus additional BNX with complete resolution of symptoms within 8 hours, and he was stabilized and discharged on BNX 24–6 mg daily.

Clinical Significance

Ketamine is a promising treatment for POW due to its potentiation of μ-opioid receptor–mediated signaling. This is the first case to describe POW in the inpatient hospital setting. More research is needed to establish the effectiveness and feasibility of ketamine as treatment for POW.