bluuebunny/crossref_metadata_2025 huggingface dataset:
Consistency Testing in WTO Law and the Special Case of Moral Regulation
Authors: Czapnik Ben
Published: February 2024

There is a debate in World Trade Organization (WTO) law about whether the right to regulate for public interest purposes is conditioned on a requirement to do so consistently. While the early Appellate Body (AB) jurisprudence eschewed consistency testing under the formal legal test, it refrained from explicitly rejecting the practice. Subsequent AB rulings have seemingly adopted a narrow type of consistency testing through the doctrine of ‘legitimate regulatory distinctions’. A case could also be made that WTO tribunals sometimes embrace consistency testing under Article XX of the General Agreement on Tariffs and Trade, although this is not explicitly acknowledged or universally recognized. In Seals, Canada explicitly attacked the European Union’s (EU) seal products ban for its lack of consistency with the EU’s broader animal welfare settings. This dispute provided an opportunity – indeed, an obligation – for the AB to establish a clear doctrine on consistency testing. This article argues that the AB shirked its duty through reasoning techniques that avoided meaningful engagement with the substance of Canada’s argument. The AB did not truly reject consistency testing, but its precise views are hard to glean due to reasoning that is opaque, confused and even contradictory. This article argues that there is a compelling case for consistency testing, at least in certain ‘public morals’ disputes, and that the AB should provide clearer guidance.
One State’s Rebel Is Another State’s Agent
Authors: Nissel Alan Tzvika
Published: February 2024

In State Responsibility and Rebels, Kathryn Greenman explores the post-colonial history of state responsibility, the doctrine of international law that determines whether a state has breached its obligations and what, if anything, can be done about it. Today, the doctrine is one of the most frequently referenced ones of international law. Greenman shows that international arbitrators have applied the rules of state responsibility in order to support a global economic order that sustains Western investments and trade. Greenman also highlights the bilateral or transactional nature of the doctrine. The early practice of state responsibility has been a story of political concessions. Western states would often withhold their recognition of governments until the latter agreed to arbitrate international claims such as injuries to aliens during the rebellions. The resulting awards were often inchoate analyses of international law, in which arbitrators would attribute liability to states for conduct that was often out of their control. These findings are as interesting as they are relevant to today’s international practice. Indeed, says Greenman, imposing state responsibility for conduct that is outside of a state’s control is effectively sustaining the legacy of international law’s colonial past.
Factors impacting complementary feeding advice given by paediatricians in Cyprus
Authors: Hileti Dona , Kokkinos Markianos
Published: February 2024

Background

Complementary feeding has long-term effects on health but there is heterogeneity in recommendations across Europe. Recommendations include responsive feeding practices and nutritional needs but there is a debate in primary paediatricians as to which one should be the main criterion for complementary feeding. This pilot study investigated (i) the factors affecting the recommendations of paediatricians in Cyprus for starting complementary feeding, (ii) whether their main criterion is the developmental readiness or the nutritional needs of the infant and (iii) how this priority influences recommendations.

Methods

The 11-item questionnaire was completed by 73 Cypriot paediatricians.

Results

Approximately 66% of paediatricians recommended starting complementary feeding between 5 and 6 months, 29% between 4 and 5 and 3% between 6 and 7 months. Predefined schemes were recommended by ∼25% of paediatricians, baby-led weaning by 14% and 58% of paediatricians recommended either modality depending on the family circumstances whilst 4% involve the mother in the decision process. Approximately 64% of paediatricians recommended the introduction of parent’s diet after the first year of life. Approximately 55% of paediatricians chose developmental readiness and 45% nutritional needs of the infant as their primary criterion for starting complementary feeding. Paediatricians who prioritized developmental readiness were more likely to be younger, less likely to advice on meat quantity and less likely to follow good nutritional practice.

Conclusions

The younger the paediatrician the more likely they are to prioritize developmental readiness over nutritional needs of the infant for complementary feeding. Paediatricians who prioritized developmental readiness were also less likely to provide nutritional advice.
Engineering of Ogataea polymorpha strains with ability for high-temperature alcoholic fermentation of cellobiose
Authors: Vasylyshyn Roksolana , Dmytruk Olena , Sybirnyy Andriy , Ruchała Justyna
Published: February 2024

Successful conversion of cellulosic biomass into biofuels requires organisms capable of efficiently utilizing xylose as well as cellodextrins and glucose. Ogataea (Hansenula) polymorpha is the natural xylose-metabolizing organism and is one of the most thermotolerant yeasts known, with a maximum growth temperature above 50°C. Cellobiose-fermenting strains, derivatives of an improved ethanol producer from xylose O. polymorpha BEP/cat8∆, were constructed in this work by the introduction of heterologous genes encoding cellodextrin transporters (CDTs) and intracellular enzymes (β-glucosidase or cellobiose phosphorylase) that hydrolyze cellobiose. For this purpose, the genes gh1-1 of β-glucosidase, CDT-1m and CDT-2m of cellodextrin transporters from Neurospora crassa and the CBP gene coding for cellobiose phosphorylase from Saccharophagus degradans, were successfully expressed in O. polymorpha. Through metabolic engineering and mutagenesis, strains BEP/cat8∆/gh1-1/CDT-1m and BEP/cat8∆/CBP-1/CDT-2mAM were developed, showing improved parameters for high-temperature alcoholic fermentation of cellobiose. The study highlights the need for further optimization to enhance ethanol yields and elucidate cellobiose metabolism intricacies in O. polymorpha yeast. This is the first report of the successful development of stable methylotrophic thermotolerant strains of O. polymorpha capable of coutilizing cellobiose, glucose, and xylose under high-temperature alcoholic fermentation conditions at 45°C.
Unrelenting Growth and Diversification: Using the Health and Retirement Study to Illuminate Cannabis Use Among Aging Americans
Authors: Kaskie Brian , Bhagianadh Divya , Bobitt Julie , Martinos Fadi , Milavetz Gary , Arora Kanika
Published: February 2024

Background and Objectives

Cannabis use among aging Americans continues to increase. We examine correlates of cannabis use including attitudes, state of residence, health status, and service use.

Research Design and Methods

Using the 2018 Health and Retirement Study Cannabis module completed by 1,372 respondents aged 50 and older, we distinguished current cannabis users from those who have never used or have some prior use. We linked 2018 and 2016 core HRS data and used multinomial regressions to identify associations among current use, attitudes, place of residence, as well as current (2018) and past (2016) medical conditions, pain, and sleep issues. We also examined associations among cannabis use, hospital stays, and outpatient medical visits.

Results

Past-year cannabis use reached 10.3% among aging Americans. Attitudes toward cannabis have changed over time with 4 of 5 survey respondents currently holding a favorable attitude. Attitude and state of residence were associated with current use. Cannabis users reported higher levels of pain, were more likely to use prescription opioids, and report activity limitations in both 2016 and 2018. Associations between cannabis use and sleep issues or concurrent healthcare use were not observed.

Discussion and Implications

Changing attitudes and state legalization appear important for late middle-aged and older persons, and as many as 1 of every 5 persons over 50 may be using cannabis by 2030. Cannabis use among aging Americans warrants increased attention from care providers, program administrators, and policymakers, especially as a prevention or harm reduction strategy relative to prescription opioids.
Untangling the complex implementation process of community-based health promotion: a multiple-case study in the Netherlands
Authors: Huiberts Irma , Singh Amika , Collard Dorine , Hendriks Mara , van Lenthe Frank, J , Chinapaw Mai
Published: February 2024

Community-based programmes are a widely implemented approach for population health promotion. Due to the context-dependent and dynamic nature of these programmes, evaluating their implementation is challenging. Identifying key events in the implementation process in evaluation could enable us to support future implementation, while acknowledging the complexity of real-world implementation. We studied the nationwide implementation of the Dutch Healthy Youth, Healthy Future (JOGG) approach, a community-based programme for childhood overweight prevention. The aims of our study were (i) to gain insights into the implementation process of the JOGG approach, and (ii) to identify key events that influenced said process. In nine communities, we conducted interviews (n = 24) with coordinators and stakeholders involved in the implementation of the JOGG approach and collected documents on the programme’s implementation. We applied the analytical tool ‘Critical Event Card’ to identify key events in the implementation process. Results showed that in 5–10 years of implementing the JOGG approach, communities have undergone different phases: preparation, upscaling, resource mobilization, integration with other policy initiatives and adaptation of the implementation strategy. Key events influencing the implementation process included national policy developments (e.g. new health programmes), framing of the JOGG approach in local policy, staff turnover and coordination teams’ experiences and actions. Furthermore, changes in implementation were often triggered by the destabilization of the implementation process and linked to opportunities for change in the policy process. The identified key events can inform future implementation of the JOGG approach as well as other community-based health promotion programmes.
Schools of clerks, schools of knights: John Grandisson and Hugh de Courtenay’s French correspondence, 1329–40
Authors: Mills Edward
Published: February 2024

The private letters within the Register of John Grandisson (bishop of Exeter, 1327–69) provide a fascinating insight into the intellectual climate of his episcopate, and attest to his strained relationship with the immensely important local magnate Hugh de Courtenay. Based on a re-examination of the manuscript Register (now held at the Devon Heritage Centre), this article offers the first modern edition and translation of a series of exchanges between the two men during Grandisson’s episcopate. Grandisson’s replies represent an assertion of clerical authority, as the two men fought over what was – in one case, literally – contested terrain.
Brahmins and Balance of Power: Re-Reading A.P. Rana's Imperatives of Non-Alignment
Authors: Thakur Vineet
Published: February 2024

In this article, I revisit a modern classic, a book that is often cited but rarely analyzed: A.P. Rana's Imperatives of Non-Alignment. Appearing in 1976, the book was a culmination of decade-long work and claimed to be the first attempt at IR theory from India. Rana was indeed from the first generation of scholars who engaged deeply with International Relation (IR) theory, and the book drew on a range of, sometimes contradictory, theoretical perspectives from Systems Theory to Realism to English School to Hindu Social Theory. In this intervention, I analyze this book and the corpus of Rana's writings with an attempt to contribute to two themes within IR. First, I show how caste plays a prominent role in Rana's thinking about Indian strategies of foreign policy behavior. His analysis makes a case for seeing nonalignment as a historical continuation of a Brahminical mode of balancing. Consequently, this article is also an effort to place caste as a central category of IR theorization from India. Secondly, I discuss the specific ways in which Rana's realism adapted to its Cold War context and advanced a redemptive vision of realism.
Modern challenges in competition enforcement and the need for clearer goals of competition law
Authors: Schwartz Ori
Published: February 2024

The debate over the goals of competition law and the standard by which to apply it have been around, more or less, ever since competition laws were first enacted. In principle, they influence every decision made by a competition enforcer or a court, whether this decision is around cartels, mergers, abuse of dominant position or even advocacy. In recent years competition authorities have been operating in an environment which is unprecedently challenging. Enforcement in digital markets and labour markets, as well as the interplay between competition and environmental policy and the green transition, shift competition enforcement to undiscovered territories. With these contemporary challenges, enforcers are far more frequently faced with the need to have a clear perception of the goal of competition law and the standard according to which to apply it to make enforcement decisions. the need for clarifying, or even redefining, the goals of competition law and the standards by which these goals are achieved, should be seriously considered by the enforcers as well as by the policy makers, who, from a democratic perspective, should be the ultimate decision makers on policy issues. The need for legal certainty presents yet another argument in the same direction.
Identifying the capabilities for creating next-generation registries: a guide for data leaders and a case for “registry science”
Authors: Labkoff Steven E , Quintana Yuri , Rozenblit Leon
Published: February 2024

Objective

The increasing demands for curated, high-quality research data are driving the emergence of a novel registry type. The need to assemble, curate, and export this data grows, and the conventional simplicity of registry models is driving the need for advanced, multimodal data registries—the dawn of the next-generation registry.

Materials and methods

The article provides an outline of the technology roles and responsibilities needed for successful implementations of next-generation registries.

Results

We propose a framework for the planning, construction, maintenance, and sustainability of this new registry type.

Discussion

A rubric of organizational, computational, and human resource needs is discussed in detail, backed by over 40 years of combined in-the-field experiences by the authors.

Conclusions

A novel field, registry science, within the clinical research informatics domain, has arisen to offer its insights into conceiving, structuring, and sustaining this new breed of tools.
Impact of Supplementing a Backgrounding Diet with Nonprotein Nitrogen on In Vitro Methane Production, Nutrient Digestibility, and Steer Performance
Authors: Vargas Juan de J , Tarnonsky Federico , Podversich Federico , Maderal Araceli , Fernandez-Marenchino Ignacio , Gómez-López Camila , Heredia Daniella , Schulmeister Tessa M , Ruiz-Ascacibar Isabel , Gonella-Diaza Angela , Ipharraguerre Ignacio R , DiLorenzo Nicolas
Published: February 2024

Two experiments were conducted to evaluate the effect of nonprotein nitrogen (NPN) supplementation on in vitro fermentation and animal performance using a backgrounding diet. In experiment 1, incubations were conducted on three separate days (replicates). Treatments were control (CTL, without NPN), urea (U), urea–biuret (UB), and urea–biuret–nitrate (UBN) mixtures. Except for control, treatments were isonitrogenous using 1% U inclusion as a reference. Ruminal fluid was collected from two Angus-crossbred steers fed a backgrounding diet plus 100 g of a UBN mixture for at least 35 d. The concentration of volatile fatty acids (VFA) and ammonia nitrogen (NH3–N), in vitro organic matter digestibility (IVOMD), and total gas and methane (CH4) production were determined at 24 h of incubation. In experiment 2, 72 Angus-crossbred yearling steers (303 ± 29 kg of body weight [BW]) were stratified by BW and randomly allocated in nine pens (eight animals/pen and three pens/treatment). Steers consumed a backgrounding diet formulated to match the diet used in the in vitro fermentation experiment. Treatments were U, UB, and UBN and were isonitrogenous using 1% U inclusion as a reference. Steers were adapted to the NPN supplementation for 17 d. Then, digestibility evaluation was performed after 13 d of full NPN supplementation for 4 d using 36 steers (12 steers/treatment). After that, steer performance was evaluated for 56 d (24 steers/treatment). In experiment 1, NPN supplementation increased the concentration of NH3–N and VFA (P < 0.01) without affecting the IVOMD (P = 0.48), total gas (P = 0.51), and CH4 production (P = 0.57). Additionally, in vitro fermentation parameters did not differ (P > 0.05) among NPN sources. In experiment 2, NPN supplementation did not change dry matter and nutrient intake (P > 0.05). However, UB and UBN showed lower (P < 0.05) nutrient digestibility than U, except for starch (P = 0.20). Dry matter intake (P = 0.28), average daily gain (P = 0.88), and gain:feed (P = 0.63) did not differ among steers receiving NPN mixtures. In conclusion, tested NPN mixtures have the potential to be included in the backgrounding diets without any apparent negative effects on animal performance and warrant further studies to evaluate other variables to fully assess the response of feeding these novel NPN mixtures.
Cattle are more motivated for a high-concentrate diet than Sudan grass hay, despite low reticulorumen pH
Authors: Coon Rachael E , Tucker Cassandra B
Published: February 2024

Subacute ruminal acidosis (SARA) is characterized by chronic low ruminal pH, and occurs for feedlot cattle fed high-concentrate diets. Forages slow digestion and reduce acid production. We aimed to assess how motivated finishing cattle are to access forage (Sudan grass hay, SG) via their willingness to interact with an electrified barrier. Reticulorumen pH was measured to relate the results to digestive health. Twenty-eight animals fed a high-concentrate ration ad libitum had access to 4 L of one of two treatments (n = 14/treatment) fed 1×/d behind a barrier: 1) SG or 2) an additional offering of the normal ration (total mixed ration [TMR]). To access their treatment, the steer voluntarily pushed his muzzle against an electrified barrier. The electrical current was increased exponentially every 24 h (0, 156, 312, 625, 1,250, 2,500, 5,000 µA) until the animal ceased accessing it. Visits to the treatment were recorded continuously 24 h/d and reticulorumen pH was measured every 10 min. Time with a reticulorumen pH below 5.8 was 348 ± 101 and 280 ± 76 min/24 h for SG and TMR animals, respectively; these durations meet the criterion for SARA. However, animals with access to SG were less likely to advance to the next current than TMR animals (P < 0.01) and were approximately 3× less willing to interact with higher currents than TMR (mean maximum current touched: 469 ± 169 and 1,380 ± 254 μA, respectively, mean ± SE, P = 0.01). Lower motivation to access SG was further demonstrated through fewer visits to the SG (2.4 ± 0.4 vs. 5.3 ± 0.6 #/d, P < 0.01), and less SG consumed than TMR (32.0 ± 0.1 vs. 74.0 ± 0.0 %/d, P < 0.01, measured as % due to weight differences of SG and TMR). Overall, finishing cattle valued the TMR more than SG, likely because of differences in the quantity offered, palatability, and familiarity. When rumen health was considered, SG animals visited more often (r = 0.5, P = 0.09) and showed fewer failed attempts (r = −0.5, P = 0.06) to access forage as the severity and duration of pH depression below 5.6, for example, increased. No measures of treatment use were related to pH depression for TMR animals (P ≥ 0.31). These findings provide evidence that cattle are motivated for Sudan grass hay when experiencing chronic low reticulorumen pH. However, they also contribute to the mixed evidence about the motivation for forage in this life stage, because, overall TMR was valued more highly than SG. Despite widespread pH depression, TMR cattle contrafreeloaded for additional concentration, demonstrating unexpectedly high motivation for this resource.
Association of glucose metabolism and insulin resistance with feed efficiency and production traits of finishing beef steers
Authors: Foote Andrew P , Salisbury Carlee M , King Mindy E , Rathert-Williams Abigail R , McConnell Hunter L , Beck Matthew R
Published: February 2024

Increasing nutrient utilization efficiency is an important component of enhancing the sustainability of beef cattle production. The objective of this experiment was to determine the association of glucose metabolism and insulin resistance with dry matter intake (DMI), average daily gain (ADG), gain:feed ratio (G:F), and residual feed intake (RFI). Steers (n = 54; initial body weight = 518 ± 27.0 kg) were subjected to an intravenous glucose tolerance test (IVGTT) where glucose was dosed through a jugular catheter and serial blood samples were collected. Three days after the last group’s IVGTT, steers began a 63-d DMI and ADG test. Body weight was measured on days 0, 1, 21, 42, 62, and 63, and DMI was measured using an Insentec Roughage Intake Control system (Hokofarm Group, Emmeloord, the Netherlands). To examine relationships between DMI, ADG, G:F, and RFI with IVGTT measurements, Pearson correlations were calculated using Proc Corr of SAS 9.4 (SAS Inst. Inc., Cary, NC). Additionally, cattle were classified based on DMI, ADG, RFI, and G:F, where the medium classification was set as mean ± 0.5 SD, the low classification was < 0.5 SD from the mean, and the high classification was > 0.5 SD from the mean. No associations between DMI and IVGTT parameters were observed, and no differences were detected when classifying cattle as having low, medium, or high DMI. Peak insulin concentration in response to the IVGTT tended to be correlated with ADG (r = 0.28; P = 0.07), indicating cattle with greater ADG tend to have a greater insulin release in response to glucose. Glucose nadir concentrations tended to be positively correlated with ADG (r = 0.26; P = 0.10). Additionally, the glucose nadir was greater in high-ADG steers (P = 0.003). The association of greater glucose nadir with high-ADG could indicate that high-ADG steers do not clear glucose as efficiently as low-ADG steers, potentially indicating increased insulin resistance. Further, RFI was not correlated with IVGTT measurements, but low RFI steers had a greater peak glucose concentration (P = 0.040) and tended to have a greater glucose area under the curve (P = 0.09). G:F was correlated with glucose area under the curve (r = 0.33; P = 0.050), glucose nadir (r = 0.35; P = 0.011), and insulin time to peak (r = 0.39; P = 0.010). These results indicate that glucose metabolism and insulin signaling are associated with growth and efficiency, but the molecular mechanisms that drive these effects need to be elucidated.
Demographic and disease-related factors impact bone turnover and vitamin D in children with hemato-oncological diseases
Authors: Jackmann Natalja , Gustafsson Jan , Utriainen Pauliina , Magnusson Per , Harila Arja , Atanasova Diana , Rinaldo Carina , Frisk Per , Mäkitie Outi
Published: February 2024

Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease.

This cross-sectional study included 165 children (91 males, median age 6.9 yr range 0.2–17.7 yr). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25OHD, PTH, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen.

Vitamin D deficiency was found in 30.9% of children. Lower 25OHD levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes −45° and 45°. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure.

In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment.
Long-term oral meclozine administration improves survival rate and spinal canal stenosis during postnatal growth in a mouse model of achondroplasia in both sexes
Authors: Funahashi Hiroto , Matsushita Masaki , Esaki Ryusaku , Mishima Kenichi , Ohkawara Bisei , Kamiya Yasunari , Takegami Yasuhiko , Ohno Kinji , Kitoh Hiroshi , Imagama Shiro
Published: February 2024

Achondroplasia (ACH) is a skeletal dysplasia characterized by short-limbed short stature caused by the gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Activated FGFR3, which is a negative regulator of bone elongation, impairs the growth of long bones and the spinal arch by inhibiting chondrocyte proliferation and differentiation. Most patients with ACH have spinal canal stenosis in addition to short stature. Meclozine has been found to inhibit FGFR3 via drug repurposing. A 10-d treatment with meclozine promoted long-bone growth in a mouse model of ACH (Fgfr3ach mice). This study aimed to evaluate the effects of long-term meclozine administration on promoting bone growth and the spinal canal in Fgfr3ach mice. Meclozine (2 mg/kg/d) was orally administered to Fgfr3ach mice for 5 d per wk from the age of 7 d to 56 d. Meclozine (2 mg/kg/d) significantly reduced the rate of death or paralysis and improved the length of the body, cranium, and long bones in male and female Fgfr3ach mice. Micro-computed tomography analysis revealed that meclozine ameliorated kyphotic deformities and trabecular parameters, including BMD, bone volume/tissue volume, trabecular thickness, and trabecular number at distal femur of Fgfr3ach mice in both sexes. Histological analyses revealed that the hypertrophic zone in the growth plate was restored in Fgfr3ach mice following meclozine treatment, suggesting upregulation of endochondral ossification. Skeletal preparations demonstrated that meclozine restored the spinal canal diameter in Fgfr3ach mice in addition to improving the length of each bone. The 2 mg/kg/d dose of meclozine reduced the rate of spinal paralysis caused by spinal canal stenosis, maintained the growth plate structure, and recovered the bone quality and growth of axial and appendicular skeletons of Fgfr3ach mice in both sexes. Long-term meclozine administration has the potential to ameliorate spinal paralysis and bone growth in patients with ACH.
Gastroscopy for dyspeptic symptoms in patients <65 years has a low yield of clinically important findings: a retrospective study
Authors: Maracle Brooke , Crick Katelynn , Novak Kerri , Campbell-Scherer Denise , Veldhuyzen van Zanten Sander , Sadowski Daniel C
Published: February 2024

Background

Dyspepsia is a common, generally low-risk gastrointestinal condition. The American College of Gastroenterology and Canadian Association of Gastroenterology recommend avoiding gastroscopy in healthy patients <60 years old. Many dyspeptic patients can be effectively managed in primary care. This study aimed to determine: (1) the proportion of gastroscopies performed for dyspepsia among patients <65 years old with no alarm symptoms or clinically appropriate indications and (2) to determine the frequency of clinically actionable findings and dyspepsia-related healthcare utilization in the year following gastroscopy.

Methods

Outpatient endoscopy reports were sampled and reviewed retrospectively from 2019 to –2021 in Edmonton, Alberta to identify gastroscopies performed for the indication of dyspepsia. Gastroscopies were considered low-risk for significant endoscopic findings if age <65, no alarm symptoms or other concerning indications, and insufficient evidence that first-line treatments and diagnostic approaches had been tried prior to gastroscopy. Clinically important findings were defined as those impacting management, not otherwise identifiable non-invasively.

Results

Of the 358 reviewed gastroscopies for dyspepsia, 293 (81.8%) had no alarm symptoms, and 130 (36.3%) had no alarm symptoms or other appropriate indications. Clinically important findings were identified in 9 (6.9%) of the 130 low-risk cases. In the year following, one patient (1/130) visited the emergency department 3 times for their symptoms and no patients required hospital admission. No malignancies were detected.

Conclusions

Many gastroscopies are performed on patients <65 years old with dyspepsia, even when they lack alarm symptoms or other clinical indications, despite recommendations against this practice and low procedure yield. Strategies to improve the uptake of current guidelines may optimize endoscopy resource utilization.
Doxycycline is a viable alternative to tetracycline for use in insect Tet-Off transgenic sexing systems, as assessed in the blowflies Cochliomyia hominivorax and Lucilia cuprina (Diptera: Calliphoridae)
Authors: Arp Alex P , Williamson Megan E , Vasquez Mario , Quintero Gladys , Vargas Lowman Aidamalia , Sagel Agustin , Scott Maxwell J
Published: February 2024

Transgenic insect strains with tetracycline repressible (Tet-Off) female-lethal genes provide significant advantages over traditional sterile insect techniques for insect population control, such as reduced diet and labor costs and more efficient population suppression. Tet-Off systems are suppressed by tetracycline-class antibiotics, most commonly tetracycline (Tc) or doxycycline (Dox), allowing for equal sex ratio colonies of transgenic insects when reared with Tc or Dox and male-only generations in their absence. Dox is a more stable molecule and has increased uptake than Tc, which could be advantageous in some insect mass-rearing systems. Here, we evaluated the suitability of Dox for rearing Tet-Off female-lethal strains of Australian sheep blowfly, Lucilia cuprina (Wiedemann, 1830) (Diptera: Calliphoridae), and New World screwworm, Cochliomyia hominivorax (Coquerel, 1858) (Diptera: Calliphoridae), and the effects of dosage on strain performance. For both species, colonies were able to be maintained with mixed-sex ratios at much lower dosages of Dox than Tc. Biological yields of C. hominivorax on either antibiotic were not significantly different. Reduction of Dox dosages in C. hominivorax diet did not affect biological performance, though rearing with 10 or 25 μg/mL was more productive than 50 μg/mL. Additionally, C. hominivorax mating performance and longevity were equal on all Dox dosages. Overall, Dox was a suitable antibiotic for mass-rearing Tet-Off female-lethal L. cuprina and C. hominivorax and was functional at much lower dosages than Tc.
A highly contiguous genome assembly for the Yellow Warbler (Setophaga petechia)
Authors: Tsai Whitney L E , Escalona Merly , Garrett Kimball L , Terrill Ryan S , Sahasrabudhe Ruta , Nguyen Oanh , Beraut Eric , Seligmann William , Fairbairn Colin W , Harrigan Ryan J , McCormack John E , Alfaro Michael E , Smith Thomas B , Bay Rachael A
Published: February 2024

The Yellow Warbler (Setophaga petechia) is a small songbird in the wood-warbler family (Parulidae) that exhibits phenotypic and ecological differences across a widespread distribution and is important to California’s riparian habitat conservation. Here, we present a high-quality de novo genome assembly of a vouchered female Yellow Warbler from southern California. Using HiFi long-read and Omni-C proximity sequencing technologies, we generated a 1.22 Gb assembly including 687 scaffolds with a contig N50 of 6.80 Mb, scaffold N50 of 21.18 Mb, and a BUSCO completeness score of 96.0%. This highly contiguous genome assembly provides an essential resource for understanding the history of gene flow, divergence, and local adaptation in Yellow Warblers and can inform conservation management of this charismatic bird species.
Multi-tissue transcriptome-wide association studies identified 235 genes for intrinsic subtypes of breast cancer
Authors: Li James L , McClellan Julian C , Zhang Haoyu , Gao Guimin , Huo Dezheng
Published: February 2024

Background

Although genome-wide association studies (GWAS) of breast cancer (BC) identified common variants which differ between intrinsic subtypes, genes through which these variants act to impact BC risk have not been fully established. Transcriptome-wide association studies (TWAS) have identified genes associated with overall BC risk, but subtype-specific differences are largely unknown.

Methods

We performed two multi-tissue TWAS for each BC intrinsic subtype, including an expression-based approach that collated TWAS signals from expression quantitative trait loci (eQTLs) across multiple tissues and a novel splicing-based approach that collated signals from splicing QTLs (sQTLs) across intron clusters and subsequently across tissues. We used summary statistics for five intrinsic subtypes including Luminal A-like, Luminal B-like, Luminal B/HER2-negative-like, HER2-enriched-like, and triple-negative BC, generated from 106 278 BC cases and 91 477 controls in the Breast Cancer Association Consortium.

Results

Overall, we identified 235 genes in 88 loci that were associated with at least one of the five intrinsic subtypes. Most genes were subtype-specific, and many have not been reported in previous TWAS. We discovered common variants that modulate expression of CHEK2 confer increased risk to Luminal A-like BC, in contrast to the viewpoint that CHEK2 primarily harbors rare, penetrant mutations. Additionally, our splicing-based TWAS provided population-level support for MDM4 splice variants that increased the risk of triple-negative BC.

Conclusion

Our comprehensive, multi-tissue TWAS corroborated previous GWAS loci for overall BC risk and intrinsic subtypes, while underscoring how common variation that impacts expression and splicing of genes in multiple tissue types can be used to further elucidate the etiology of BC.
(Mal)adaptive sibling self and other communicative resilience in the context of parental substance use
Authors: Nolan-Cody Haley , Scharp Kristina M
Published: February 2024

Managing parental substance use disorder (SUD) within the family context is a collaborative effort. For families with multiple children, the sibling relationship might be one source of support for dealing with this stressor. Findings from a sample of adult siblings with parents with SUD highlighted that they (a) experience five resilience triggers, (b) utilize self and other communicative resilience (CR) processes, and (c) experience a tensional process in which CR can be both adaptive, maladaptive, and simultaneously both. Overall, we advance the communication theory of resilience by (a) being the first to apply the other-resilience heuristic, (b) exploring relationships between self-resilience and other-resilience, (c) introducing a new CR tension, and (d) discussing the potential benefit of engaging in what we call strategic resilience. By analyzing the resilience processes of adult siblings experiencing parental SUD, we also recommend practical applications for social workers, providers, and counselors.
Non-foliar photosynthesis and nitrogen assimilation influence grain yield in durum wheat regardless of water conditions
Authors: Vicente Rubén , Vergara-Díaz Omar , Uberegui Estefanía , Martínez-Peña Raquel , Morcuende Rosa , Kefauver Shawn C , López-Cristoffanini Camilo , Aparicio Nieves , Serret María Dolores , Araus José Luis
Published: February 2024

There is a need to generate improved crop varieties adapted to the ongoing changes in the climate. We studied durum wheat canopy and central metabolism of six different photosynthetic organs in two yield-contrasting varieties. The aim was to understand the mechanisms associated with the water stress response and yield performance. Water stress strongly reduced grain yield, plant biomass, and leaf photosynthesis, and down-regulated C/N-metabolism genes and key protein levels, which occurred mainly in leaf blades. By contrast, higher yield was associated with high ear dry weight and lower biomass and ears per area, highlighting the advantage of reduced tillering and the consequent improvement in sink strength, which promoted C/N metabolism at the whole plant level. An improved C metabolism in blades and ear bracts and N assimilation in all photosynthetic organs facilitated C/N remobilization to the grain and promoted yield. Therefore, we propose that further yield gains in Mediterranean conditions could be achieved by considering the source–sink dynamics and the contribution of non-foliar organs, and particularly N assimilation and remobilization during the late growth stages. We highlight the power of linking phenotyping with plant metabolism to identify novel traits at the whole plant level to support breeding programmes.
The maternal embrace: the protection of plant embryos
Authors: Woudenberg Sjoerd , Hadid Feras , Weijers Dolf , Borassi Cecilia
Published: February 2024

All land plants—the embryophytes—produce multicellular embryos, as do other multicellular organisms, such as brown algae and animals. A unique characteristic of plant embryos is their immobile and confined nature. Their embedding in maternal tissues may offer protection from the environment, but also physically constrains development. Across the different land plants, a huge discrepancy is present between their reproductive structures whilst leading to similarly complex embryos. Therefore, we review the roles that maternal tissues play in the control of embryogenesis across land plants. These nurturing, constraining, and protective roles include both direct and indirect effects. In this review, we explore how the maternal surroundings affect embryogenesis and which chemical and mechanical barriers are in place. We regard these questions through the lens of evolution, and identify key questions for future research.
Excessive iron deposition in root apoplast is involved in growth arrest of roots in response to low pH
Authors: Fang Xian Zhi , Xu Xiao Lan , Ye Zheng Qian , Liu Dan , Zhao Ke Li , Li Dong Ming , Liu Xing Xing , Jin Chong Wei
Published: February 2024

The rhizotoxicity of protons (H+) in acidic soils is a fundamental constraint that results in serious yield losses. However, the mechanisms underlying H+-mediated inhibition of root growth are poorly understood. In this study, we revealed that H+-induced root growth inhibition in Arabidopsis depends considerably on excessive iron deposition in the root apoplast. Reducing such aberrant iron deposition by decreasing the iron supply or disrupting the ferroxidases LOW PHOSPHATE ROOT 1 (LPR) and LPR2 attenuates the inhibitory effect of H+ on primary root growth efficiently. Further analysis showed that excessive iron deposition triggers a burst of highly reactive oxygen species, consequently impairing normal root development. Our study uncovered a valuable strategy for improving the ability of plants to tolerate H+ toxicity by manipulating iron availability.
Rapid polarization variations in the O4 supergiant ζ Puppis
Authors: Bailey Jeremy , Howarth Ian D , Cotton Daniel V , Kedziora-Chudczer Lucyna , De Horta Ain , Martell Sarah L , Eldridge Colin , Luckas Paul
Published: February 2024

We present time-series linear-polarization observations of the bright O4 supergiant ζ Puppis. The star is found to show polarization variation on time-scales of around an hour and longer. Many of the observations were obtained contemporaneously with Transiting Exoplanet Survey Satellite (TESS) photometry. We find that the polarization varies on similar time-scales to those seen in the TESS light curve. The previously reported 1.78-d photometric periodicity is seen in both the TESS and polarization data. The amplitude ratio of photometry to polarization is ∼9 for the periodic component and the polarization variation is oriented along position angle ∼70°–160°. Higher frequency stochastic variability is also seen in both data sets with an amplitude ratio of ∼19 and no preferred direction. We model the polarization expected for a rotating star with bright photospheric spots and find that models that fit the photometric variation produce too little polarization variation to explain the observations. We suggest that the variable polarization is more likely the result of scattering from the wind, with corotating interaction regions producing the periodic variation and a clumpy outflow producing the stochastic component. The Hα emission line strength was seen to increase by 10 per cent in 2021 with subsequent observations showing a return to the pre-2018 level.
An extreme ultra-compact X-ray binary in a globular cluster: multiwavelength observations of RZ 2109 explored in a triple system framework
Authors: Dage Kristen C , Bahramian Arash , Naoz Smadar , Bobrick Alexey , Athukoralalage Wasundara , Brumback McKinley C , Haggard Daryl , Kundu Arunav , Zepf Stephen E
Published: February 2024

The globular cluster ultraluminous X-ray source, RZ 2109, is a complex and unique system that has been detected at X-ray, ultraviolet, and optical wavelengths. Based on almost 20 yr of Chandra and XMM–Newton observations, the X-ray luminosity exhibits order of magnitude variability, with the peak flux lasting on the order of a few hours. We perform robust time series analysis on the archival X-ray observations and find that this variability is periodic on a time-scale of 1.3 ± 0.04 d. The source also demonstrates broad [O iii] λ5007 emission, which has been observed since 2004, suggesting a white dwarf donor and therefore an ultra-compact X-ray binary. We present new spectra from 2020 and 2022, marking 18 yr of observed [O iii] emission from this source. Meanwhile, we find that the globular cluster counterpart is unusually bright in the NUV/UVW2 band. Finally, we discuss RZ 2109 in the context of the eccentric Kozai–Lidov mechanism and show that the observed 1.3 d periodicity can be used to place constraints on the tertiary configuration, ranging from 20 min (for a 0.1 M⊙ companion) to approximately 95 min (for a 1 M⊙ companion), if the eccentric Kozai–Lidov mechanism is at the origin of the periodic variability.
Rapid and Repeated Climate Adaptation Involving Chromosome Inversions following Invasion of an Insect
Authors: Ma Li-Jun , Cao Li-Jun , Chen Jin-Cui , Tang Meng-Qing , Song Wei , Yang Fang-Yuan , Shen Xiu-Jing , Ren Ya-Jing , Yang Qiong , Li Hu , Hoffmann Ary Anthony , Wei Shu-Jun
Published: February 2024

Following invasion, insects can become adapted to conditions experienced in their invasive range, but there are few studies on the speed of adaptation and its genomic basis. Here, we examine a small insect pest, Thrips palmi, following its contemporary range expansion across a sharp climate gradient from the subtropics to temperate areas. We first found a geographically associated population genetic structure and inferred a stepping-stone dispersal pattern in this pest from the open fields of southern China to greenhouse environments of northern regions, with limited gene flow after colonization. In common garden experiments, both the field and greenhouse groups exhibited clinal patterns in thermal tolerance as measured by critical thermal maximum (CTmax) closely linked with latitude and temperature variables. A selection experiment reinforced the evolutionary potential of CTmax with an estimated h2 of 6.8% for the trait. We identified 3 inversions in the genome that were closely associated with CTmax, accounting for 49.9%, 19.6%, and 8.6% of the variance in CTmax among populations. Other genomic variations in CTmax outside the inversion region were specific to certain populations but functionally conserved. These findings highlight rapid adaptation to CTmax in both open field and greenhouse populations and reiterate the importance of inversions behaving as large-effect alleles in climate adaptation.
How snoRNAs can contribute to cancer at multiple levels
Authors: Zacchini Federico , Barozzi Chiara , Venturi Giulia , Montanaro Lorenzo
Published: February 2024

snoRNAs are a class of non-coding RNAs known to guide site specifically RNA modifications such as 2′-O-methylation and pseudouridylation. Recent results regarding snoRNA alterations in cancer has been made available and suggest their potential evaluation as diagnostic and prognostic biomarkers. A large part of these data, however, was not consistently confirmed and failed to provide mechanistic insights on the contribution of altered snoRNA expression to the neoplastic process. Here, we aim to critically review the available literature on snoRNA in cancer focusing on the studies elucidating the functional consequences of their deregulation. Beyond the canonical guide function in RNA processing and modification we also considered additional roles in which snoRNA, in various forms and through different modalities, are involved and that have been recently reported.
SAMHD1 expression contributes to doxorubicin resistance and predicts survival outcomes in diffuse large B-cell lymphoma patients
Authors: Daddacha Waaqo , Monroe Dominique , Schlafstein Ashley J , Withers Allison E , Thompson Elizabeth B , Danelia Diana , Luong Nho C , Sesay Fatmata , Rath Sandip K , Usoro Edidiong R , Essien Mark E , Jung Andrew T , Jiang Jinmeng G , Hu Jiaxuan , Mahboubi Bijan , Williams Arilyn , Steinbeck Julia E , Yang Xiaofeng , Buchwald Zachary S , Dynan William S , Switchenko Jeffrey M , Kim Baek , Khan Mohammad K , Jaye David L , Yu David S
Published: February 2024

Diffuse large B-cell lymphoma (DLBCL) is a commonly diagnosed, aggressive non-Hodgkin's lymphoma. While R-CHOP chemoimmunotherapy is potentially curative, about 40% of DLBCL patients will fail, highlighting the need to identify biomarkers to optimize management. SAMHD1 has a dNTPase-independent role in promoting resection to facilitate DNA double-strand break (DSB) repair by homologous recombination. We evaluated the relationship of SAMHD1 levels with sensitivity to DSB-sensitizing agents in DLBCL cells and the association of SAMHD1 expression with clinical outcomes in 79 DLBCL patients treated with definitive therapy and an independent cohort dataset of 234 DLBCL patients. Low SAMHD1 expression, Vpx-mediated, or siRNA-mediated degradation/depletion in DLBCL cells was associated with greater sensitivity to doxorubicin and PARP inhibitors. On Kaplan–Meier log-rank survival analysis, low SAMHD1 expression was associated with improved overall survival (OS), which on subset analysis remained significant only in patients with advanced stage (III-IV) and moderate to high risk (2–5 International Prognostic Index (IPI)). The association of low SAMHD1 expression with improved OS remained significant on multivariate analysis independent of other adverse factors, including IPI, and was validated in an independent cohort. Our findings suggest that SAMHD1 expression mediates doxorubicin resistance and may be an important prognostic biomarker in advanced, higher-risk DLBCL patients.