bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproductive Markers of Testicular Function and Size During Puberty in Boys With and Without a History of Cryptorchidism
Authors: Rodprasert Wiwat , Koskenniemi Jaakko J , Virtanen Helena E , Sadov Sergey , Perheentupa Antti , Ollila Helena , Albrethsen Jakob , Andersson Anna-Maria , Juul Anders , Skakkebaek Niels E , Main Katharina M , Toppari Jorma 
Published: September 2022

Abstract

Context
Longitudinal data on levels of hypothalamic-pituitary-gonadal axis hormones and insulin-like growth factor I (IGF-I) during puberty in boys with a history of cryptorchidism are largely missing.

Objective
We aimed to compare pubertal hormone levels between boys with a history of congenital cryptorchidism who experienced spontaneous testicular descent or underwent orchiopexy and boys without a history of cryptorchidism.

Methods
This was a nested case-control study within a population-based birth cohort, with a prospective, longitudinal pubertal follow-up every 6 months (2005 to 2019). Participants were 109 Finnish boys, including boys with a history of unilateral cryptorchidism who underwent orchiopexy (n = 15), unilateral cryptorchidism who had spontaneous testicular descent (n = 15), bilateral cryptorchidism who underwent orchiopexy (n = 9), bilateral cryptorchidism who had spontaneous testicular descent (n = 7), and controls (n = 63). Serum reproductive hormone levels and testicular volumes were measured.

Results
From around onset of puberty, boys with bilateral cryptorchidism who underwent orchiopexy had significantly higher follicle-stimulating hormone (FSH) and lower inhibin B levels than controls. Boys with unilateral cryptorchidism who underwent orchiopexy had significantly higher FSH than controls, whereas inhibin B levels were similar. Testosterone, luteinizing hormone, insulin-like factor 3, and IGF-I were generally similar between groups. Testicular volume of boys with unilateral or bilateral cryptorchidism who underwent orchiopexy was smaller than that of the controls from 1 year after pubertal onset (P &lt; 0.05).

Conclusion
Cryptorchid boys, particularly those with bilateral cryptorchidism who underwent orchiopexy, had altered levels of serum biomarkers of Sertoli cells and germ cells and smaller testicular volumes compared with controls.
Premature Ovarian Insufficiency in CLPB Deficiency: Transcriptomic, Proteomic and Phenotypic Insights
Authors: Tucker Elena J , Baker Megan J , Hock Daniella H , Warren Julia T , Jaillard Sylvie , Bell Katrina M , Sreenivasan Rajini , Bakhshalizadeh Shabnam , Hanna Chloe A , Caruana Nikeisha J , Wortmann Saskia B , Rahman Shamima , Pitceathly Robert D S , Donadieu Jean , Alimi Aurelia , Launay Vincent , Coppo Paul , Christin-Maitre Sophie , Robevska Gorjana , van den Bergen Jocelyn , Kline Brianna L , Ayers Katie L , Stewart Phoebe N , Stroud David A , Stojanovski Diana , Sinclair Andrew H 
Published: September 2022

Abstract

Context
Premature ovarian insufficiency (POI) is a common form of female infertility that usually presents as an isolated condition but can be part of various genetic syndromes. Early diagnosis and treatment of POI can minimize comorbidity and improve health outcomes.

Objective
We aimed to determine the genetic cause of syndromic POI, intellectual disability, neutropenia, and cataracts.

Methods
We performed whole-exome sequencing (WES) followed by functional validation via RT-PCR, RNAseq, and quantitative proteomics, as well as clinical update of previously reported patients with variants in the caseinolytic peptidase B (CLPB) gene.

Results
We identified causative variants in CLPB, encoding a mitochondrial disaggregase. Variants in this gene are known to cause an autosomal recessive syndrome involving 3-methylglutaconic aciduria, neurological dysfunction, cataracts, and neutropenia that is often fatal in childhood; however, there is likely a reporting bias toward severe cases. Using RNAseq and quantitative proteomics we validated causation and gained insight into genotype:phenotype correlation. Clinical follow-up of patients with CLPB deficiency who survived to adulthood identified POI and infertility as a common postpubertal ailment.

Conclusion
A novel splicing variant is associated with CLPB deficiency in an individual who survived to adulthood. POI is a common feature of postpubertal female individuals with CLPB deficiency. Patients with CLPB deficiency should be referred to pediatric gynecologists/endocrinologists for prompt POI diagnosis and hormone replacement therapy to minimize associated comorbidities.
Aldosterone-Producing Adenomas of Increased Size Are Associated With Higher Steroidogenic Activity
Authors: Nakai Kazuki , Manaka Katsunori , Sato Junichiro , Takeuchi Maki , Yamazaki Yuto , Sasano Hironobu , Tsurutani Yuya , Saito Jun , Nishikawa Tetsuo , Iiri Taroh , Nangaku Masaomi , Makita Noriko 
Published: September 2022

Abstract

Context
There are inconsistent results and insufficient evidence as to whether an association exists between the size and aldosterone-producing ability of aldosterone-producing adenomas.

Objective
We further investigated this possible association retrospectively.

Methods
A total of 142 cases of primary aldosteronism diagnosed as unilateral by adrenal venous sampling at 2 referral centers between 2009 and 2019 were included. We classified these individuals into small and large tumor groups using a diameter of 14 mm as a cutoff. This size was the median diameter of the tumor on the affected side of the adrenal gland. We compared plasma aldosterone concentration (PAC), plasma renin activity (PRA), PAC to PRA ratio, PAC from a saline infusion test (SIT), urinary aldosterone secretion (uAld), and serum potassium as indices of aldosterone-producing ability between the 2 groups. In some cases, we conducted histopathological evaluations and detection of the KCNJ5 mutation.

Results
PAC, PAC to PRA ratio, PAC from SIT, and uAld were higher and serum potassium was lower in the large tumor group. PAC, PAC from SIT, uAld, and serum potassium significantly correlated with tumor diameter. PRA was not associated with tumor diameter. Clear cell–dominant cases were more common in the large tumor group, while cases showing a strong expression of CYP11B2 were not significantly different between the groups. KCNJ5 mutations tended to be more common in the large tumor group.

Conclusion
The higher aldosterone-producing ability in larger adenomas can be used to infer the responsible lesion and disease type.
Cilia proteins getting to work – how do they commute from the cytoplasm to the base of cilia?
Authors: Hibbard Jaime V. K. , Vázquez Neftalí , Wallingford John B. 
Published: September 2022

ABSTRACT
Cilia are multifunctional organelles that originated with the last eukaryotic common ancestor and play central roles in the life cycles of diverse organisms. The motile flagella that move single cells like sperm or unicellular organisms, the motile cilia on animal multiciliated cells that generate fluid flow in organs, and the immotile primary cilia that decorate nearly all cells in animals share many protein components in common, yet each also requires specialized proteins to perform their specialized functions. Despite a now-advanced understanding of how such proteins are transported within cilia, we still know very little about how they are transported from their sites of synthesis through the cytoplasm to the ciliary base. Here, we review the literature concerning this underappreciated topic in ciliary cell biology. We discuss both general mechanisms, as well as specific examples of motor-driven active transport and passive transport via diffusion-and-capture. We then provide deeper discussion of specific, illustrative examples, such as the diverse array of protein subunits that together comprise the intraflagellar transport (IFT) system and the multi-protein axonemal dynein motors that drive beating of motile cilia. We hope this Review will spur further work, shedding light not only on ciliogenesis and ciliary signaling, but also on intracellular transport in general.
Achieving sustainable transformation in science – green grassroots groups need nurturing from the top
Authors: Dobbelaere Jeroen , Heidelberger Jan B. , Borgermann Nikoline 
Published: September 2022

ABSTRACT
Climate change is the greatest challenge of our time, and drastic climate action is needed urgently across industries and sectors to prevent the worst in terms of consequences. Although academic research brings great benefits to society, it leaves behind a considerable environmental footprint at the same time. This is particularly true for lab research within the life sciences. To reduce the climate impact of academic research, both bottom-up and top-down strategies are necessary. On the bottom-up side, ‘green’ grassroots groups are emerging in academia, but most institutions fail to nurture and harness their potential for driving change. We report findings from a survey of 63 such grassroots groups operating in academic environments, highlighting that their main challenges in making research more sustainable include lack of time, budget, involvement in management decisions and support from management. For the first time, we map the inception, goals and structure of green grassroots groups in academia and outline concrete steps in overcoming barriers to harvest their full potential, thus making academic research fit for the future.
Defects in division plane positioning in the root meristematic zone affect cell organization in the differentiation zone
Authors: Mills Alison M. , Rasmussen Carolyn G. 
Published: September 2022

ABSTRACT
Cell-division-plane orientation is critical for plant and animal development and growth. TANGLED1 (TAN1) and AUXIN-INDUCED IN ROOT CULTURES 9 (AIR9) are division-site-localized microtubule-binding proteins required for division-plane positioning. The single mutants tan1 and air9 of Arabidopsis thaliana have minor or no noticeable phenotypes, but the tan1 air9 double mutant has synthetic phenotypes including stunted growth, misoriented divisions and aberrant cell-file rotation in the root differentiation zone. These data suggest that TAN1 plays a role in non-dividing cells. To determine whether TAN1 is required in elongating and differentiating cells in the tan1 air9 double mutant, we limited its expression to actively dividing cells using the G2/M-specific promoter of the syntaxin KNOLLE (pKN:TAN1–YFP). Unexpectedly, in addition to rescuing division-plane defects, expression of pKN:TAN1–YFP rescued root growth and cell file rotation defects in the root-differentiation zone in tan1 air9 double mutants. This suggests that defects that occur in the meristematic zone later affect the organization of elongating and differentiating cells.
Estimation of microtubule-generated forces using a DNA origami nanospring
Authors: Nick Maleki Ali , Huis in 't Veld Pim J. , Akhmanova Anna , Dogterom Marileen , Volkov Vladimir A. 
Published: September 2022

ABSTRACT
Microtubules are dynamic cytoskeletal filaments that can generate forces when polymerizing and depolymerizing. Proteins that follow growing or shortening microtubule ends and couple forces to cargo movement are important for a wide range of cellular processes. Quantifying these forces and the composition of protein complexes at dynamic microtubule ends is challenging and requires sophisticated instrumentation. Here, we present an experimental approach to estimate microtubule-generated forces through the extension of a fluorescent spring-shaped DNA origami molecule. Optical readout of the spring extension enables recording of force production simultaneously with single-molecule fluorescence of proteins getting recruited to the site of force generation. DNA nanosprings enable multiplexing of force measurements and only require a fluorescence microscope and basic laboratory equipment. We validate the performance of DNA nanosprings against results obtained using optical trapping. Finally, we demonstrate the use of the nanospring to study proteins that couple microtubule growth and shortening to force generation.
Foxc1 and Foxc2 are indispensable for the maintenance of nephron and stromal progenitors in the developing kidney
Authors: Motojima Masaru , Tanaka Masayuki , Kume Tsutomu 
Published: September 2022

ABSTRACT
Nephron development proceeds with reciprocal interactions among three layers: nephron progenitors (NPs), ureteric buds and stromal progenitors (SPs). We found that Foxc1 and Foxc2 (Foxc1/2) are expressed in NPs and SPs. Systemic deletion of Foxc1/2 2 days after the onset of metanephros development (embryonic day 13.5) resulted in the epithelialization of NPs and ectopic formation of renal vesicles. NP-specific deletion did not cause these phenotypes, indicating that Foxc1/2 in other cells (likely in SPs) contributed to the maintenance of NPs. Single-cell RNA-sequencing analysis revealed the existence of NP and SP subpopulations, the border between committed NPs and renewing NPs, and similarity between the cortical interstitium and vascular smooth muscle type cells. Integrated analysis of the control and Foxc1/2 knockout data indicated transformation of some NPs to strange cells expressing markers of the vascular endothelium, reduced numbers of self-renewing NP and SP populations, and downregulation of crucial genes for kidney development, such as Fgf20 and Frem1 in NPs, and Foxd1 and Sall1 in SPs. It also revealed upregulation of genes that were not usually expressed in NPs and SPs. Thus, Foxc1/2 maintain NPs and SPs by regulating the expression of multiple genes.
Release of HIV-1 particles from macrophages is promoted by an anchored cytoskeleton and driven by mechanical constraints
Authors: Rodrigues Vasco , Taheraly Sarah , Maurin Mathieu , San-Roman Mabel , Granier Emma , Hanouna Anaël , Benaroch Philippe 
Published: September 2022

ABSTRACT
A feature of HIV-1 replication in macrophages is that viral assembly occurs at the limiting membrane of a compartment often named the virus-containing compartment (VCC). Assembled virions accumulate in the lumen of the VCC, from where they can be released into the extracellular medium via mechanisms that remain poorly described. Here, we show that the actin cytoskeleton contributes to this process by performing experiments combining pharmacological and mechanical perturbations with imaging and biochemical analysis. We found that jasplakinolide inhibited HIV-1 release from macrophages and led to scattering of the compartment. Concomitantly, both the integrin CD18 (β2-integrin) and the phosphorylated form of PYK2 (also known as PTK2B) were displaced away from the VCC. Inhibition of PYK2 activity promoted retention of viral particles in VCCs that lost their connections to the surface. Finally, in infected macrophages undergoing frustrated phagocytosis, VCCs rapidly trafficked to the basal membrane and released their viral content, in a manner dependent on their association with the actin cytoskeleton. These results highlight that the trafficking of VCCs and virus release are intimately linked to a reorganization of the macrophage actin cytoskeleton that can be modulated by external physical cues.
Sea turtle hatchlings can distinguish between coastal and oceanic seawaters
Authors: Soeiro Gabriel , Mendes da Silva Eduardo , Leduc Antoine O. H. C. 
Published: September 2022

ABSTRACT
Following their emergence on land, sea turtle hatchlings need to travel through the open ocean. Whether hatchlings can detect ecologically and functionally relevant chemical cues released in the marine habitat is unknown. We collected seawater at 6 and 27 km off the Brazilian coast, i.e. within and beyond the continental shelf. In a two-choice flume, we exposed post-emergent (&lt;24 h old) loggerhead (Caretta caretta) turtles to these seawaters. Based on their life history, we posited that if hatchlings could distinguish between the seawater from these regions, they should prefer the oceanic seawater and/or avoid the coastal seawater. Hatchlings were tested singly and could access any parts of the flume. We recorded the seawater plume first visited and the time spent in each plume. Of all the first choices and time spent in a plume, nearly 70% involved the oceanic seawater. The ability of hatchlings to distinguish between seawaters could provide goal-recognition information.
The Impact of Committing to Customer Orders in Online Retail
Authors: Figueira Gonçalo , van Jaarsveld Willem , Amorim Pedro , Fransoo Jan C. 
Published: September 2022

Problem definition: Online retailers are on a consistent drive to increase on-time delivery and reduce customer lead time. However, in reality, an increasing share of consumers places orders early. Academic/practical relevance: Such advance demand information can be deployed strategically to reduce costs and improve the customer service experience. This requires inventory and allocation policies that make optimal use of this information and that induce consumers to place their orders early. An increasing number of online retailers not only offer customers a choice of lead time but also, actively back-order missing items from a consumer basket. Methodology: We develop new allocation policies that commit to a customer order upon arrival of the order rather than at the moment the order is due. We provide analytical results for the performance of these allocation policies and evaluate their behavior with real data from a large food retailer. Results: Our policy leads to a higher fill rate at the expense of a slight increase in average delay. The analysis based on real-life data suggests a sizeable impact that should impact current best practices in online retail. Managerial implications: With the changing landscape in online retail, customers increasingly place baskets of orders that they would like to receive at a planned and confirmed moment in time. Especially in grocery, this has grown fast. This fundamentally changes the strategic management of inventory. We demonstrate that online retailers should commit early to customer orders to enhance the customer service experience and eventually, to also create opportunities for reducing the cost of operations. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2022.1124 .
The Promise of mHealth for Chronic Disease Management Under Different Payment Systems
Authors: Rajan Balaraman , Sainathan Arvind , Agnihothri Saligrama , Cui Leon 
Published: September 2022

Problem definition: Rapid innovations in technology have created opportunities for different modes of healthcare delivery including digital services provided via mobile applications (mHealth). mHealth technology has the potential to provide efficient, effective, and patient-centered healthcare to manage chronic conditions. However, the economics associated with the adoption and integration of mHealth into the care delivery process is not well understood. In a chronic care clinical practice setting, we investigate fee-for-service (FFS) and capitation payment systems, and explore their performance in a traditional office-visit mode and in a mHealth-adopted mode. We identify conditions under which it is preferable to switch to an mHealth-based practice from an office visit-based practice. Methodology/results: We use an analytical model to track the progression of a chronic disease and formulate an optimization problem in which the clinic decides the time between scheduled visits and patient panel size. We consider many patient-doctor interaction factors including the risk-index of patients, the cost of being sick, and the effectiveness of treatment. We measure the performance based on four different criteria: physician net revenue, physician panel size, total patient utility, and payor net revenue. Although patients may find mHealth mode to be very beneficial, physicians under an FFS system may only adopt mHealth for moderately risky patients but for neither low-risk nor high-risk patients. Capitation clinics are likely to adopt mHealth (higher net revenue) even if the technology is moderately effective. Importantly, mHealth is preferred by patients (higher total utility) and policy makers (greater coverage) when the clinic serves moderate-risk or high-risk patients. Managerial implications: Chronic conditions need continuous care management and use of mHealth has been very promising. However, adoption of mHealth by healthcare providers has been very slow. Our research explores payment systems, physician incentives, and optimal conditions for mHealth to achieve its full potential. Supplemental Material: The e-companion is available at https://doi.org/10.1287/msom.2022.1143 .
A Meta-Analysis of Instructional Management Models Affecting Creative Thinking Development
Authors: Ayutthaya Tanapat Itsarangkul Na , Damrongpanit Suntonrapot 
Published: September 2022

<p style="text-align: justify;">The main objective of this research was to study the effects of instructional management models and nominal variables on the development of students’ creative thinking. The researchers used the research synthesis of 400 studies on the development of students' creative thinking by a meta-analysis of research according to Cohen. The meta-analysis results revealed that the average effect size of the instructional management model (d = 3.43; [3.10, 3.17]) was positive and had a very high effect size with statistical significance. The most significant influence on the creative thinking development model was creative development theory (d = 4.217; [3.32, 5.11]). In addition, effect sizes varied with the attribute variables of the research, particularly the attribute variable of the research on instruction with the highest effect consisted of research with the focus on language, at the primary level, applied Torrance's creativity theory, designed between one to six lesson plans. Moreover, there was less than one hour per plan, the instructional period including the experiment conducted more than 31 hours and there were four weeks of instruction. In addition, there were six steps for instruction, there had quiz as an assessment tool, number of exams varied between 30 and 39 questions, and knowledge sheets were used as instructional materials. In the context of the meta-analysis, the findings indicated that the teachers should apply creative development theory in developing the students’ creative thinking for more effective instructional management.</p>