bluuebunny/crossref_metadata_2025 huggingface dataset:
A low crosstalk seven-core five-mode fiber for high density transmission and large capacity communication
Authors: Wang Luyao , Li Shuguang , Shao Pengshuai , Liu Qiang , Yang Gang , Li Xiang
Published: April 2024

We propose a seven-core five-mode fiber with air hole-assisted and high refractive index ring structure, and it can be fabricated by the stack-and-draw technique. The air hole auxiliary structure can significantly restrain the energy coupling between cores, and the high refractive index ring structure can meet the requirements of low intra-core crosstalk (XT) by improving the effective refractive index difference (Δn

eff
) between adjacent modes. Through analyzing the influence of the number and arrangement of air holes on inter-core XT and effective mode field area (A

eff
), it can be achieved the results that the inter-core XT is less than −44 dB/100 km and all the A

eff
values of LP modes are greater than 100 μm2 in the seven-core five-mode fiber when the wavelength is 1550 nm and the bending radius (R) is 80 mm. At the same time, the Δn

eff
between LP21 and LP02 mode can be controlled to 1.3 × 10−3 by adjusting the parameters of the high refractive index ring. In addition, the relative core multiplexing factor (RCMF) of the seven-core five-mode fiber is as high as 88.34. The simulation results show that the seven-core five-mode fiber has high spatial density and is suitable for the communication system with multi-channel and long-distance transmission.
Coupled surface diffusion and mean curvature motion: An axisymmetric system with two grains and a hole
Authors: Golubkov Katrine , Novick-Cohen Amy , Vaknin Yotam
Published: April 2024

Thin polycrystalline solid state films, which are used in many technological applications, can exhibit various phenomena, such as wetting, dewetting, and hole formation. We focus on a model system containing two contacting grains which surround a hole. For simplicity, the system is assumed to be axisymmetric, to be supported by a planar substrate and to be bounded within an inert semi-infinite cylinder. We assume that the exterior surfaces of the grains evolve by surface diffusion and the grain boundary between the adjacent grains evolve by motion by mean curvature. Boundary conditions are imposed following W.W. Mullins, 1958. Parametric formulas are derived for the steady states, which contain two nodoids describing the exterior surfaces, which are coupled to a catenoid which describes the grain boundary. At steady state, the physical parameters of the system may be prescribed via two angles,

β
\beta

, the angle between the exterior surface and the grain boundary, and

θ
c

\theta _c

, the contact angle between the exterior surface and the substrate; additionally, there are two dimensionless geometric parameters which must satisfy certain constraints. We prove that if

β
∈
(
π

/

2
,
π
)

\beta \in (\pi /2, \pi )

and

θ
c

=
π

\theta _c=\pi

, then there exists a continuum of steady states. Numerical calculations indicate that steady state profiles can exhibit physical features, such as hillock formation; a fuller numerical study of the steady states and their properties recently appeared in Zigelman and Novick-Cohen [J. Appl. Phys. 134 (2023), 135302], which relies on the formulas and results derived here.
Challenges of acute pain management in older patients
Authors: Almodibeg Bader , Forget Patrice
Published: April 2024

Adequate management of acute pain in the older population is crucial. However, it is inherently complex because of multiple physiological changes that significantly impact both the pharmacokinetics and pharmacodynamics of medications. Current guidelines promote paracetamol as the first-line analgesic for acute pain in older adults, whereas opioids are advised cautiously for moderate to severe acute pain. However, opioids come with a significant array of side effects, which can be more pronounced in older individuals. Ketamine administered via intranasal (IN) and nebulised inhalation in the emergency department for managing acute pain in older patients shows promising potential for improving pain management and reducing opioid reliance Kampan, Thong-on, Sri-on (2024, Age Ageing, 53, afad255). Nebulised ketamine appears superior in terms of adverse event incidence. However, the adoption of IN or nebulised ketamine in older adult acute pain management remains unclear because of the lack of definitive conclusions and clear guidelines. Nevertheless, these modalities can be valuable options for patients where opioid analgesics are contraindicated or when intravenous morphine titration is impractical or contraindicated. Here, we review these concepts, the latest evidence and propose avenues for research.
Lifestyle-related factors in late midlife as predictors of frailty from late midlife into old age: a longitudinal birth cohort study
Authors: Haapanen Markus J , Mikkola Tuija M , Jylhävä Juulia , Wasenius Niko S , Kajantie Eero , Eriksson Johan G , von Bonsdorff Mikaela B
Published: April 2024

Background

Few studies have examined longitudinal changes in lifestyle-related factors and frailty.

Methods

We examined the association between individual lifestyle factors (exercise, diet, sleep, alcohol, smoking and body composition), their sum at baseline, their change over the 17-year follow-up and the rate of change in frailty index values using linear mixed models in a cohort of 2,000 participants aged 57–69 years at baseline.

Results

A higher number of healthy lifestyle-related factors at baseline was associated with lower levels of frailty but not with its rate of change from late midlife into old age. Participants who stopped exercising regularly (adjusted β × Time = 0.19, 95%CI = 0.10, 0.27) and who began experiencing sleeping difficulties (adjusted β × Time = 0.20, 95%CI = 0.10, 0.31) experienced more rapid increases in frailty from late midlife into old age. Conversely, those whose sleep improved (adjusted β × Time = −0.10, 95%CI = −0.23, −0.01) showed a slower increase in frailty from late midlife onwards. Participants letting go of lifestyle-related factors (decline by 3+ factors vs. no change) became more frail faster from late midlife into old age (adjusted β × Time = 0.16, 95% CI = 0.01, 0.30).

Conclusions

Lifestyle-related differences in frailty were already evident in late midlife and persisted into old age. Adopting one new healthy lifestyle-related factor had a small impact on a slightly less steeply increasing level of frailty. Maintaining regular exercise and sleeping habits may help prevent more rapid increases in frailty.
Integration of electronic project management software in an investigational drug service pharmacy within an academic medical center
Authors: Hill Cameron , Froerer Camryn
Published: April 2024

Purpose

An investigational drug services (IDS) pharmacy plays a vital role in supporting clinical trial research by ensuring the safe and efficient management of investigational products. This article describes the implementation of an electronic project management software to improve an IDS pharmacy’s study protocol work. The article describes the implementation of the software and how this approach addressed specific challenges, including project oversight, process standardization, documentation, reporting, accountability, and intrateam communication.

We describe an electronic project management software system used to streamline and standardize the work associated with study protocols. This software provides an organized and customizable workspace to manage tasks associated with each study protocol. The software automates task creation, tracks progress, and ensures comprehensive record keeping. Additionally, the software fosters effective communication within the team and offers real-time reporting to assess team productivity and progress. We have observed improved consistency, enhanced revenue, including approximately $18,000 in additional fee capture, and increased collaboration among pharmacy team members.

Conclusion

Implementing an electronic project management software has proven highly beneficial in the IDS pharmacy. The software has significantly improved workflow efficiency by addressing challenges in study protocol management. While initial setup and training required time and resources, the long-term benefits in project oversight, collaboration, and revenue capture justify the investment. An electronic project management software is a valuable tool in managing the complexity of study protocol activities and supports the pharmacy’s crucial role in advancing clinical research.
Narrative Skills in Mandarin–English Dual Language Immersion Learners
Authors: Pace Amy , Lü Chan , Guo Laura X , Zhou Jieyu
Published: April 2024

This article investigated the development of narrative production skills among Mandarin-English dual language immersion (DLI) students. A total of 60 children in first (N = 20), third (N = 21), and fifth-sixth (N = 19) grades generated oral narratives from wordless picture books in Mandarin and English. We examined variability in children’s macrostructure and microstructure production by language and grade level. We also examined within-language associations and cross-language transfer in narrative skills. Children in higher grades incorporated more macrostructure and microstructure elements in their narratives than children in lower grades. Within each language, microstructure skills were correlated with macrostructure skills. Evidence for development of shared skills across languages and language-specific patterns of narrative skills were also identified. Results contribute to the growing body of evidence for facilitative transfer in immersion contexts and highlight the importance of measuring outcomes in both the societal and the partner language.
Chemical modification of Arthrobacter sarcosine oxidase by N-methylisothiazolinone reduces reactivity toward oxygen
Authors: Toyama Fuka , Kimura Hironori , Zhang Yuqi , Nishiya Yoshiaki
Published: March 2024

N-Methylisothiazolinone (MIT) is a thiol group modifier and antimicrobial agent. Arthrobacter sarcosine oxidase (SoxA), a diagnostic enzyme for assaying creatinine, loses its activity upon the addition of MIT, and its inactivation mechanism remains unclear. In this study, SoxA was chemically modified using MIT (mo-SoxA), and its structural and chemical properties were characterized. Spectral analysis data, oxygen consumption rates, and reactions were compared between intact SoxA and mo-SoxA. These demonstrate that the oxidative half-reaction toward oxygen is inhibited by MIT modification. The oxidase activity of mo-SoxA was approximately 2.1% of that of intact SoxA, and its dehydrogenase activity was approximately 4.2 times higher. The C-to-S mutants revealed that cooperative modification of 2 specific cysteine residues caused a drastic change in the enzyme reaction mode. Based on the modeled tertiary structures, the putative entrance for oxygen uptake is predicted to be blocked by the chemical modification of the 2 cysteine residues.
Skin keratinocyte-derived SIRT1 and BDNF modulate mechanical allodynia in mouse models of diabetic neuropathy
Authors: O’Brien Jennifer , Niehaus Peter , Chang Koping , Remark Juliana , Barrett Joy , Dasgupta Abhishikta , Adenegan Morayo , Salimian Mohammad , Kevas Yanni , Chandrasekaran Krish , Kristian Tibor , Chellappan Rajeshwari , Rubin Samuel , Kiemen Ashley , Lu Catherine Pei-Ju , Russell James W , Ho Cheng-Ying
Published: March 2024

Diabetic neuropathy is a debilitating disorder characterized by spontaneous and mechanical allodynia. The role of skin mechanoreceptors in the development of mechanical allodynia is unclear. We discovered that mice with diabetic neuropathy had decreased sirtuin 1 (SIRT1) deacetylase activity in foot skin, leading to reduced expression of brain-derived neurotrophic factor (BDNF) and subsequent loss of innervation in Meissner corpuscles, a mechanoreceptor expressing the BDNF receptor TrkB. When SIRT1 was depleted from skin, the mechanical allodynia worsened in diabetic neuropathy mice, likely due to retrograde degeneration of the Meissner-corpuscle innervating Aβ axons and aberrant formation of Meissner corpuscles which may have increased the mechanosensitivity. The same phenomenon was also noted in skin-keratinocyte specific BDNF knockout mice. Furthermore, overexpression of SIRT1 in skin induced Meissner corpuscle reinnervation and regeneration, resulting in significant improvement of diabetic mechanical allodynia.

Overall, the findings suggested that skin-derived SIRT1 and BDNF function in the same pathway in skin sensory apparatus regeneration and highlighted the potential of developing topical SIRT1-activating compounds as a novel treatment for diabetic mechanical allodynia.
Synthesis and evaluation of modified polyhedral oligomeric silsesquioxane (POSS) derivatives with luminescent Side-chains having charge-transfer characters
Authors: Sato Keita , Gon Masayuki , Tanaka Kazuo , Chujo Yoshiki
Published: April 2024

We describe here a synthesis and evaluation of polyhedral oligomeric silsesquioxane (POSS) derivatives having luminescent charge-transfer molecules. The electron withdrawing groups (EWG), such as trifluoromethyl groups, and electron donating groups (EDG), such as methoxy and dimethylamine groups, were introduced into π-conjugated systems connected at each vertex of the silica cube, and their optical properties were evaluated in solution and solid states. It was shown that the POSS scaffold hardly influenced the electronic structures of each substituent, meanwhile there were significant differences in electronic interactions between EWGs and EDGs depending on the order of connections from the silica cube. Finally, we obtained heat resistant luminescent materials having intermolecular charge-transfer characteristics.
Visualization and exploration of linked data using virtual reality
Authors: Kellmann Alexander J , Postema Max , de Keijser Joris , Svetachov Pjotr , Wilson Rebecca C , van Enckevort Esther J , Swertz Morris A
Published: March 2024

In this report, we analyse the use of virtual reality (VR) as a method to navigate and explore complex knowledge graphs. Over the past few decades, linked data technologies [Resource Description Framework (RDF) and Web Ontology Language (OWL)] have shown to be valuable to encode such graphs and many tools have emerged to interactively visualize RDF. However, as knowledge graphs get larger, most of these tools struggle with the limitations of 2D screens or 3D projections. Therefore, in this paper, we evaluate the use of VR to visually explore SPARQL Protocol and RDF Query Language (SPARQL) (construct) queries, including a series of tutorial videos that demonstrate the power of VR (see Graph2VR tutorial playlist: https://www.youtube.com/playlist?list=PLRQCsKSUyhNIdUzBNRTmE-_JmuiOEZbdH). We first review existing methods for Linked Data visualization and then report the creation of a prototype, Graph2VR. Finally, we report a first evaluation of the use of VR for exploring linked data graphs. Our results show that most participants enjoyed testing Graph2VR and found it to be a useful tool for graph exploration and data discovery. The usability study also provides valuable insights for potential future improvements to Linked Data visualization in VR.
Maltose accumulation-induced cell death in Saccharomyces cerevisiae
Authors: Zhang Xiaohuan , Nijland Jeroen G , Driessen Arnold J M
Published: April 2024

Pretreatment of lignocellulose yields a complex sugar mixture that potentially can be converted into bioethanol and other chemicals by engineered yeast. One approach to overcome competition between sugars for uptake and metabolism is the use of a consortium of specialist strains capable of efficient conversion of single sugars. Here, we show that maltose inhibits cell growth of a xylose-fermenting specialist strain IMX730.1 that is unable to utilize glucose because of the deletion of all hexokinase genes. The growth inhibition cannot be attributed to a competition between maltose and xylose for uptake. The inhibition is enhanced in a strain lacking maltase enzymes (dMalX2) and completely eliminated when all maltose transporters are deleted. High-level accumulation of maltose in the dMalX2 strain is accompanied by a hypotonic-like transcriptional response, while cells are rescued from maltose-induced cell death by the inclusion of an extracellular osmolyte such as sorbitol. These data suggest that maltose-induced cell death is due to high levels of maltose uptake causing hypotonic-like stress conditions and can be prevented through engineering of the maltose transporters. Transporter engineering should be included in the development of stable microbial consortia for the efficient conversion of lignocellulosic feedstocks.
Modified differential lysis for sexual assault samples using a combined enzymatic and alkaline approach
Authors: Hudson Brittany C , Dawson Green Tracey
Published: April 2024

Sexual assault sample processing, despite recent funding and research efforts, remains time-consuming, labourious, and inefficient. These limitations, combined with the prevalence of sexual assaults, have prompted the need to develop a cheaper, quicker, and more robust method for separating victim and perpetrator contributions within sexual assault evidence so that analysts can keep pace with submissions and cases can be resolved in a timely manner. Thus, this study examined the use of a combined enzymatic and alkaline approach for differential cell lysis—with the goal of developing a quick, cheap, and more efficient DNA isolation method. Quantification results for this assay revealed that (72.0 ± 18.3)%, (15.8 ± 14.2)%, and (29.5 ±  23.7)% of total DNA were retained in sperm fractions for neat semen, neat vaginal, and semen–vaginal mixture eluates, respectively. Short tandem repeat (STR) analysis of mixture samples processed with this technique exhibited sperm fraction DNA profiles with mean male-to-female ratios of 1.74:1, which was a 3.01 ± 2.30-fold improvement in male-to-female ratios and led to the recovery of 5.90 ± 7.80 unshared male contributor alleles in sperm fractions that were otherwise undetected in unseparated controls. Overall, this study presented a modified differential lysis approach using prepGEM™ and sodium hydroxide treatments that can accomplish cell elution and fractional lysis within 25 min. Future studies should investigate alternative “non-sperm” cell lysis methods to enhance lysis efficiency and minimize the potential for inhibition, as well as the optimization and automation of this technique.

Key points
Activity Diversity and Well-Being in Daily Life: Evidence for Heterogeneity Between Older Adults
Authors: Luo Minxia , Moulder Robert Glenn , Breitfelder Laura K , Röcke Christina
Published: March 2024

Objectives

Although higher activity diversity is associated with higher well-being at the between-person level, it is unknown whether a day with higher activity diversity is related to higher well-being within persons. Within 24 hr per day, there are a limited number of activities on which individuals could spend their time and energy. Personal resources could influence the expenditure of energy and thus the experience with daily activities. This study examined daily associations between activity diversity and well-being and whether age and self-related health moderated the associations.

Methods

For seven times per day over 2 weeks, 129 retired older adults (Mage = 73.9 years, SDage = 5.6) reported their present activity engagement and positive and negative affect. Daily activity diversity was operationalized as the number of different activity types reported per day. Daily positive and negative affect were assessed as the average of a range of high- and low-arousal affective states. Self-rated health was assessed with an item from the 12-Item Short-Form Health Survey at baseline.

Results

Multilevel models showed that daily activity diversity was unrelated, on average, to daily positive or negative affect at the between- and within-person levels. Daily activity diversity was associated with lower daily positive affect in participants with lower self-rated health, but the Johnson-Neyman regions of significance were outside of the range of observed data.

Discussion

Divergent patterns were observed in the within-person associations between activity diversity and well-being across participants. Results are discussed in the context of time use and well-being in older age.
Widowhood and mortality risk in Taiwan: a population-based matched cohort study
Authors: Wang Shi-Heng , Wu Huijing , Hsu Le-Yin , Lin Mei-Chen , Fan Chun-Chieh , Chen Pei-Chun , Hsu Chih-Cheng , Wu Chi-Shin
Published: March 2024

Background

Studying the causes of death among deceased spouses and surviving partners may provide insights into the underlying mechanisms of the association between widowhood and mortality. This study investigated the mortality risk of widowhood in Taiwan, examined the association of the cause of death between widowed individuals and their deceased spouses and explored potential modifying effects by age, gender and duration after widowhood.

Methods

This matched cohort study utilized Taiwan's National Health Insurance claims database and National Death Registry. In total, 204 010 widowed men and 596 136 widowed women were identified with a mean follow-up period of 6.9 and 7.9 years, respectively, and 816 040 comparison men and 2 384 544 comparison women were selected.

Results

Widowhood was associated with an increased mortality risk, with widowed men having a 1.32 increased risk and widowed women having a 1.27 increased risk. Age at spousal death and duration modified the associations after widowhood. The widowed individuals are more likely to die by the same cause as the deceased spouse if they died by suicide, accident, endocrine, gastrointestinal disorders or infection.

Conclusions

The study suggests that healthcare policies and interventions should be developed to improve widowed individuals' health and overall welfare.
Power data prediction method of new energy system based on wavelet transform and adaptive hybrid optimization
Authors: Xiong Shanxia , Zhang Fan , Zhou Zhi , Zeng Yadong
Published: March 2024

New energy power generation is easily affected by climate, seasons, holidays and other factors, and has different fluctuation characteristics. Aiming at the problems of low prediction accuracy and weak generalization ability of power data with different characteristics, a new energy generation data prediction method based on wavelet transform and adaptive hybrid optimization is proposed. First, the power data is transformed by wavelets to obtain sequencing of different types of information. Then LSTM model and autoregressive moving average model are used to fit and predict different sequences. Finally, the prediction sequence is reconstructed to obtain the prediction result of the power data. This method takes the actual data of a power system as the data set, which not only has high prediction accuracy, but also has strong generalization ability.
Diagnosis and Risk Factors of Prediabetes and Diabetes in People Living With Human Immunodeficiency Virus: Evaluation of Clinical and Microbiome Parameters
Authors: Bar Ziv Omer , Cahn Avivit , Jansen Tallulah , Istomin Valery , Kedem Eynat , Olshtain-Pops Karen , Israel Sarah , Oster Yonatan , Orenbuch-Harroch Efrat , Korem Maya , Strahilevitz Jacob , Levy Itzchak , Valdés-Mas Rafael , Ivanova Valeria , Elinav Eran , Shahar Eduardo , Elinav Hila
Published: April 2024

Diabetes mellitus (DM) is more common among people living with human immunodeficiency virus (PLWH) compared with healthy individuals. In a prospective multicenter study (N = 248), we identified normoglycemic (48.7%), prediabetic (44.4%), and diabetic (6.9%) PLWH. Glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG) sensitivity in defining dysglycemia was 96.8%, while addition of oral glucose tolerance test led to reclassification of only 4 patients. Inclusion of 93 additional PLWH with known DM enabled identification of multiple independent predictors of dysglycemia or diabetes: older age, higher body mass index, Ethiopian origin, HIV duration, lower integrase inhibitor exposure, and advanced disease at diagnosis. Shotgun metagenomic microbiome analysis revealed 4 species that were significantly expanded with hyperglycemia/hyperinsulinemia, and 2 species that were differentially more prevalent in prediabetic/diabetic PLWH. Collectively, we uncover multiple potential host and microbiome predictors of altered glycemic status in PLWH, while demonstrating that FBG and HbA1c likely suffice for diabetes screening. These potential diabetic predictors merit future prospective validation.
Colonial Redress and the Unintended Consequences of Global Opportunities
Authors: Kim Claudia Junghyun
Published: March 2024

Research shows that the rise of political and discursive opportunities enabled by the diffusion of progressive global norms has empowered many aggrieved local actors. Drawing on colonial victims’ transnational redress movements, I add to this literature in two ways. First, rejecting the common association between global opportunities and local movement facilitation and success, I make a counterintuitive argument that the early availability of opportunities can inadvertently hamper a movement’s efficacy in achieving its goals in the long run. Second, contrary to the implicit assumption that large-scale, high-profile transnational movements should fare better than smaller, little-known ones, I demonstrate that the latter can sometimes achieve their goals more easily than the former. In making these arguments, I show that an increasing focus in the norm literature on backlash in target states against norm promotion risks neglecting the flip side of the same coin: Global normative support inadvertently undermining the efficacy of local causes it otherwise helps publicize. Empirically, I look at three Korean colonial victim groups and their divergent paths to transnational redress.
Integrase strand transfer inhibitor resistance mediated by R263K plus E157Q in a patient with HIV infection treated with bictegravir/tenofovir alafenamide/emtricitabine: case report and review of the literature
Authors: Buzon-Martin Luis , Navarro-San Francisco Carolina , Fernandez-Regueras María , Sanchez-Gomez Leticia
Published: April 2024

Objectives

The in vivo selection of E157Q plus R263K has not been reported in patients treated with coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). To the best of our knowledge, we hereby report the first case of high-grade INSTI resistance associated with the presence of these aminoacidic substitutions in a treatment-experienced HIV patient treated with BIC/FTC/TAF.

Methods

Clinical case report and review of the literature.

Results

A heavily treatment-experienced patient was switched to BIC/FTC/TAF due to drug–drug interactions after being diagnosed with disseminated Mycobacterium avium-intracellulare disease. He had been treated before with raltegravir with poor adherence. No mutations in the integrase gene were detected 1 year after finishing treatment with raltegravir. Months after being switched to BIC/FTC/TAF, and again with poor adherence documented, virological failure (VF) was detected. The polymorphic substitution E157Q and the resistance mutation R263K in the integrase gene were detected, as well as M184V, among other mutations in the reverse transcriptase gene. The patient is currently being treated with dolutegravir q12h plus boosted darunavir along with directly observed treatment, and for the first time in 20 years, plasmatic viral load values are below 100 copies/mL.

Conclusions

This case illustrates that the combination of E157Q and R263K plus M184V can be selected in vivo in a clinical scenario of poor adherence with BIC/FTC/TAF, although it is a very rare phenomenon. Previous VF with first-generation integrase strand transfer inhibitors (INSTIs) should be kept in mind when switching patients to second-generation INSTIs.
Characterizing sow feed intake during lactation to explain litter and subsequent farrowing performance
Authors: Estrada Jorge , Johnson Danielle C , Kyle Kelsey L , Perez Jeremy , Parr Eric , Welch Michael W , Neill Casey , Peterson Beau A , Boler Dustin D
Published: April 2024

Variation in feed intake results in nearly 20% of sows consuming less than the recommended lysine (Lys) intake for lactating sows. The Lys requirement for lactating sows is based on litter size and piglet average daily gain which influences milk production. Litter size continues to increase every year causing the need for routine reevaluation of nutrient requirements. If dietary inclusion levels are not continuously adjusted this can lead to inadequate daily Lys and energy intake and may negatively impact sow body condition and litter performance. The objective was to characterize the average daily feed intake (ADFI) of sows and define feed intake patterns and their effects on sow body weight, farrowing performance, litter performance, and subsequent farrowing performance. ADFI during lactation was recorded for 4,248 sows from 7 independent research studies. Data collection occurred from November 2021 through November 2023 at a commercial breed-to-wean facility in western Illinois. Each sow was categorized as: consistently low intake (< 5.5 kg/d) throughout the lactation (LLL); low intakes (< 5 kg/d) in the first week, then gradually increased throughout the rest of the lactation period (LHH); gradual increase in intake throughout lactation with no drop and a peak intake after day 10 of lactation (gradual); rapid increase in intake with no drop and the peak intake met before day 10 (rapid); a major drop in feed intake (> 1.6 kg decrease for ≥ 2 d) any time during lactation (MAJOR); minor drop (≤ 1.6 kg for ≥ 2 d; MINOR). Sows were also separated into low (quartile 1; ≤ 25%), average (quartile 2 through 3), or high feed intake (quartile 4; ≥ 75%) by parity (P1, P2, P3+). Sows in the LLL category were younger in parity, had the greatest preweaned mortality, weaned the lightest average pigs, and experienced the greatest loss in body weight percentage compared with sows in all other feed intake categories. Furthermore, sows in the LLL and LHH categories had one fewer subsequent pig born compared with sows in the other four categories. These data support historical findings that feed intake patterns directly contribute to current litter farrowing performance. Lactation intake patterns also influence subsequent farrowing performance. Identifying under-consuming sows that are likely Lys and energy deficient allows producers opportunities to promote consistent, adequate daily intakes to these groups and mitigate negative impacts on sow and litter performance.
Comparisons of in-hospital fee and surgical outcomes between robot-assisted, laparoscopic, and open radical cystectomy: a Japanese nationwide study
Authors: Yokoyama Minato , Chen Wei , Waseda Yuma , Fujiwara Motohiro , Kato Daisuke , Shirakawa Takeshi , Shimizu Yohei , Nenohi Tsunehiro , Matsumoto Yuki , Okumura Taisuke , Urushibara Masayasu , Ai Masumi , Fushimi Kiyohide , Fukagai Takashi , Eto Masatoshi , Fujii Yasuhisa , Ishizaka Kazuhiro
Published: March 2024

Objective

To evaluate in-hospital fees and surgical outcomes of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC) using a Japanese nationwide database.

Methods

All data were obtained from the Diagnosis Procedure Combination database between April 2020 and March 2022. Basic characteristics and perioperative indicators, including in-hospital fees, were compared among the RARC, LRC and ORC groups. Propensity score–matched comparisons were performed to assess the differences between RARC and ORC.

Results

During the study period, 2931, 1311 and 2435 cases of RARC, LRC and ORC were identified, respectively. The RARC group had the lowest in-hospital fee (median: 2.38 million yen), the shortest hospital stay (26 days) and the lowest blood transfusion rate (29.5%), as well as the lowest complication rate (20.9%), despite having the longest anesthesia time (569 min) among the three groups (all P < 0.01). The outcomes of LRC were comparable with those of RARC, and the differences in these indicators between the RARC and ORC groups were greater than those between the RARC and LRC groups. In propensity score–matched comparisons between the RARC and ORC groups, the differences in the indicators remained significant (all P < 0.01), with an ~50 000 yen difference in in-hospital fees.

Conclusions

RARC and LRC were considered to be more cost-effective surgeries than ORC due to their superior surgical outcomes and comparable surgical fees in Japan. The widespread adoption of RARC and LRC is expected to bring economic benefits to Japanese society.
The Dynamics of Disease: Toward a Processual Theory of Health
Authors: Nielsen Thor Hennelund
Published: April 2024

The following article presents preliminary reflections on a processual theory of health and disease. It does this by steering the discussion more toward an ontology of organisms rather than conceptual analysis of the semantic content of the terms “health” and “disease.” In the first section, four meta-theoretical assumptions of the traditional debate are identified and alternative approaches to the problems are presented. Afterwards, the view that health and disease are constituted by a dynamic relation between demands imposed on an organism and individual presuppositions for adequate response is developed. In the last section, the paper takes stock of three possible objections to and clarifies some implications of this approach to the notions of health and disease.
Prediction of cognitive decline in older breast cancer survivors: the Thinking and Living with Cancer study
Authors: McDeed Arthur Patrick , Van Dyk Kathleen , Zhou Xingtao , Zhai Wanting , Ahles Tim A , Bethea Traci N , Carroll Judith E , Cohen Harvey Jay , Nakamura Zev M , Rentscher Kelly E , Saykin Andrew J , Small Brent J , Root James C , Jim Heather , Patel Sunita K , Mcdonald Brenna C , Mandelblatt Jeanne S , Ahn Jaeil
Published: April 2024

Purpose

Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment.

Methods

We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function.

Results

Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score.

Conclusions

Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings.
The crystal structure of bacteriophage λ RexA provides novel insights into the DNA binding properties of Rex-like phage exclusion proteins
Authors: Adams Myfanwy C , Schiltz Carl J , Sun Jing , Hosford Christopher J , Johnson Virginia M , Pan Hao , Borbat Peter P , Freed Jack H , Thomason Lynn C , Court Carolyn , Court Donald L , Chappie Joshua S
Published: March 2024

RexA and RexB function as an exclusion system that prevents bacteriophage T4rII mutants from growing on Escherichia coli λ phage lysogens. Recent data established that RexA is a non-specific DNA binding protein that can act independently of RexB to bias the λ bistable switch toward the lytic state, preventing conversion back to lysogeny. The molecular interactions underlying these activities are unknown, owing in part to a dearth of structural information. Here, we present the 2.05-Å crystal structure of the λ RexA dimer, which reveals a two-domain architecture with unexpected structural homology to the recombination-associated protein RdgC. Modelling suggests that our structure adopts a closed conformation and would require significant domain rearrangements to facilitate DNA binding. Mutagenesis coupled with electromobility shift assays, limited proteolysis, and double electron–electron spin resonance spectroscopy support a DNA-dependent conformational change. In vivo phenotypes of RexA mutants suggest that DNA binding is not a strict requirement for phage exclusion but may directly contribute to modulation of the bistable switch. We further demonstrate that RexA homologs from other temperate phages also dimerize and bind DNA in vitro. Collectively, these findings advance our mechanistic understanding of Rex functions and provide new evolutionary insights into different aspects of phage biology.
The RNA secondary structure of androgen receptor-FL and V7 transcripts reveals novel regulatory regions
Authors: Rouse Warren B , Tompkins Van S , O’Leary Collin A , Moss Walter N
Published: March 2024

The androgen receptor (AR) is a ligand-dependent nuclear transcription factor belonging to the steroid hormone nuclear receptor family. Due to its roles in regulating cell proliferation and differentiation, AR is tightly regulated to maintain proper levels of itself and the many genes it controls. AR dysregulation is a driver of many human diseases including prostate cancer. Though this dysregulation often occurs at the RNA level, there are many unknowns surrounding post-transcriptional regulation of AR mRNA, particularly the role that RNA secondary structure plays. Thus, a comprehensive analysis of AR transcript secondary structure is needed. We address this through the computational and experimental analyses of two key isoforms, full length (AR-FL) and truncated (AR-V7). Here, a combination of in-cell RNA secondary structure probing experiments (targeted DMS-MaPseq) and computational predictions were used to characterize the static structural landscape and conformational dynamics of both isoforms. Additionally, in-cell assays were used to identify functionally relevant structures in the 5′ and 3′ UTRs of AR-FL. A notable example is a conserved stem loop structure in the 5′UTR of AR-FL that can bind to Poly(RC) Binding Protein 2 (PCBP2). Taken together, our results reveal novel features that regulate AR expression.
Ribosomal RNA modification enzymes stimulate large ribosome subunit assembly in E. coli
Authors: Ero Rya , Leppik Margus , Reier Kaspar , Liiv Aivar , Remme Jaanus
Published: March 2024

Ribosomal RNA modifications are introduced by specific enzymes during ribosome assembly in bacteria. Deletion of individual modification enzymes has a minor effect on bacterial growth, ribosome biogenesis, and translation, which has complicated the definition of the function of the enzymes and their products. We have constructed an Escherichia coli strain lacking 10 genes encoding enzymes that modify 23S rRNA around the peptidyl-transferase center. This strain exhibits severely compromised growth and ribosome assembly, especially at lower temperatures. Re-introduction of the individual modification enzymes allows for the definition of their functions. The results demonstrate that in addition to previously known RlmE, also RlmB, RlmKL, RlmN and RluC facilitate large ribosome subunit assembly. RlmB and RlmKL have functions in ribosome assembly independent of their modification activities. While the assembly stage specificity of rRNA modification enzymes is well established, this study demonstrates that there is a mutual interdependence between the rRNA modification process and large ribosome subunit assembly.
Survival and treatment outcomes in patients with leptomeningeal disease from metastatic melanoma
Authors: Saberian Chantal , Milton Denái R , Simon Julie , Amaria Rodabe N , Diab Adi , McQuade Jennifer , Patel Sapna P , Tawbi Hussein , Yee Cassian , Wong Michael K , McCutcheon Ian E , Davies Michael A , Ferguson Sherise D , Glitza Oliva Isabella C
Published: March 2024

Background

Melanoma leptomeningeal disease (LMD) has a poor prognosis. However, the management of patients with advanced melanoma has evolved with time, including those with LMD. We reviewed a large cohort of melanoma LMD patients to assess factors associated with survival.

Methods

Retrospective clinical data was collected on patients diagnosed with LMD at MD Anderson Cancer Center from 2015 to 2020. Overall survival (OS) was determined from LMD diagnosis to date of death or last follow-up. The Kaplan–Meier method and log-rank test were used to estimate OS and to assess univariate group differences, respectively. Multivariable associations of survival with variables of interest were determined using Cox proportional hazards regression models.

Results

A total of 172 patients were identified. The median age at LMD diagnosis was 53 (range 20–79) years, and all patients had radiographic evidence of LMD on magnetic resonance imaging of either brain or spine. In total 143 patients previously received systemic therapy (83%), with a median of 2 prior treatments (range 0–5). 81 patients (47%) had concurrent uncontrolled systemic disease and 80 patients (53%) had elevated serum LDH at the time of diagnosis. With a median follow-up of 4.0 months (range 0.1–65.3 months), median OS for all patients from LMD diagnosis was 4.9 months. Patients (n = 45) who received intrathecal therapy or systemic immunotherapy for LMD had a median OS of 8.0 months and 10.2 months, respectively. On multivariable analysis, decreased performance status, positive CSF cytology, elevated LDH, and whole brain radiation were associated with worse OS.

Conclusions

Despite many advances in therapeutic options, the outcomes of melanoma patients with LMD remains poor. However, a subset of patients appears to derive benefit from LMD-directed treatment.
Observation of quantum oscillations near the Mott-Ioffe-Regel limit in CaAs3
Authors: Wang Yuxiang , Zhao Minhao , Zhang Jinglei , Wu Wenbin , Li Shichao , Zhang Yong , Jiang Wenxiang , Joseph Nesta Benno , Xu Liangcai , Mou Yicheng , Yang Yunkun , Leng Pengliang , Zhang Yong , Pi Li , Suslov Alexey , Ozerov Mykhaylo , Wyzula Jan , Orlita Milan , Zhu Fengfeng , Zhang Yi , Kou Xufeng , Zhu Zengwei , Narayan Awadhesh , Qian Dong , Wen Jinsheng , Yuan Xiang , Xiu Faxian , Zhang Cheng
Published: March 2024

The Mott-Ioffe-Regel limit sets the lower bound of the carrier mean free path for coherent quasiparticle transport. Metallicity beyond this limit is of great interest because it is often closely related to quantum criticality and unconventional superconductivity. Progress along this direction mainly focuses on the strange-metal behaviors originating from the evolution of the quasiparticle scattering rate, such as linear-in-temperature resistivity, while the quasiparticle coherence phenomena in this regime are much less explored due to the short mean free path at the diffusive bound. Here we report the observation of quantum oscillations from Landau quantization near the Mott-Ioffe-Regel limit in CaAs3. Despite the insulator-like temperature dependence of resistivity, CaAs3 presents giant magnetoresistance and prominent Shubnikov–de Haas oscillations from Fermi surfaces, indicating highly coherent band transport. In contrast, quantum oscillation is absent in the magnetic torque. The quasiparticle effective mass increases systematically with magnetic fields, manifesting a much larger value than what is expected based on magneto-infrared spectroscopy. This suggests a strong many-body renormalization effect near the Fermi surface. We find that these unconventional behaviors may be explained by the interplay between the mobility edge and the van Hove singularity, which results in the formation of coherent cyclotron orbits emerging at the diffusive bound. Our results call for further study on the electron correlation effect of the van Hove singularity.
Effects of increasing dietary arginine supply during the three first weeks after weaning on pig growth performance, plasma amino acid concentrations, and health status
Authors: Perez-Palencia Jorge Y , Ramirez-Camba Christian D , Haydon Keith , Urschel Kristine L , Levesque Crystal L
Published: April 2024

A total of 425 weaned pigs (Exp. 1: 225 pigs [5.8 ± 0.9 kg]; Exp. 2: 200 pigs [6.1 ± 1.2 kg]) were used to determine the optimal dietary standardized ileal digestible (SID) arginine (Arg) level in early nursery diets based on growth and health responses. The basal diet in Exp.1 was formulated to meet SID Arg recommendation (0.66%; NRC, 2012) and in Exp. 2, SID Arg was set to simulate current industry practices for feeding nursery pigs (1.15 %). Basal diets were supplemented with 0.3%, 0.6%, 0.9%, and 1.2% of l-arginine to provide five levels of dietary SID Arg. Experimental diets were fed during phases I (days 0 to 7) and II (days 8 to 21) with common diets until market. Feed disappearance and body weight (BW) were measured on days 7, 14, 21, and 43. Final BW was recorded at first removal of pigs for market. Pen fecal score was assigned daily from days 0 to 21. Plasma immunoglobulin A (IgA) was determined on days 0, 7, and 14 and amino acids (AAs) concentration and plasma urea nitrogen (PUN) on days 0 and 14. Orthogonal polynomial contrasts were used to determine the linear and quadratic effects of dietary Arg. Optimal SID Arg was determined by fitting the data with piecewise regression, using growth performance as the primary response variable. In Exp. 1, dietary Arg linearly increased (P < 0.1) BW, average daily gain (ADG), and gain to feed ratio (G:F) ratio on day 21, as well as reduced (χ2 = 0.004) the percentage of pigs that lost weight (PLW) in week 1 by 29%. Dietary Arg resulted in linear improvement (P = 0.082) of ADG for the overall nursery period and quadratic improvement (P < 0.1) of final BW at marketing. In Exp. 2, dietary Arg linearly increased (P < 0.05) ADG and average daily feed intake (ADFI) in week 1, BW and ADFI (P < 0.1) on day 14, as well as reduced (χ2 ≤ 0.001) PLW in week 1. From days 0 to 21, G:F was improved quadratically (P < 0.1). Dietary Arg linearly increased (P < 0.1) ADG and BW on day 43. Dietary Arg supplementation decreased the incidence (χ2 < 0.05) of soft and watery feces during the first weeks after weaning and lower concentration of plasma IgA on days 7 and 14. Dietary Arg linearly and/or quadratically influenced plasma AA concentrations (P < 0.05), including an increase in Arg, Leu, Phe, Val, citrulline, ornithine, and PUN concentrations. Overall, weaned pigs exhibit optimal nursery growth performance and health when provided with dietary SID Arg ranging from 1.5% to 1.9%. This dietary range contributes to a reduction in the occurrence of fall-back pigs and improvements in final BW at marketing.