bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-directional trafficking of the IFT25 protein in the developing mouse sperm flagella
Authors: Li Wei , Niu Changmin , Yap Yi Tian , Li Tao , Zheng Cheng , Goswami Mariska , Kandiraju Sanjana , Dhikhirullahi Opeyemi , Xu Jie , Zhang Jifeng , Kelly Christopher V , Zhang Zhibing 
Published: November 2024

Abstract
Intraflagellar transport 25 is a component of the intraflagellar transport 25-B complex. In mice, even though this intraflagellar transport component is not required for cilia formation in somatic cells, it is essential for sperm formation. However, the intracellular localization of this protein in male germ cells is not known given no reliable antibodies are available for histologic studies, and the dynamic trafficking in the developing sperm flagella is not clear. To examine localization of the protein in male germ cells and further investigate the mechanism of intraflagellar transport in sperm formation, particularly to look into the dynamic trafficking of the protein, we generated a mouse intraflagellar transport 25–green fluorescent protein knock-in mouse model using the clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats associated protein 9 system, with the mouse intraflagellar transport 25 protein fused with a green fluorescent protein tag in the C-terminus. Three independent lines were analyzed. Western blotting using both anti-intraflagellar transport 25 and anti-green fluorescent protein antibodies showed that the intraflagellar transport 25–green fluorescent protein fusion protein was highly abundant only in the testis, which is consistent with the endogenous intraflagellar transport 25 protein. Examination of localization of the intraflagellar transport 25–green fluorescent protein in isolated germ cells revealed that the fusion protein was present in the cytoplasm of spermatocytes and round spermatids and a strong signal was present in the developing sperm flagellar. The homozygous knock-in mice had normal spermatogenesis, fertility and sperm parameters. Diffusion analysis of intraflagellar transport 25 within the developing flagellar revealed the presence of both mobile and immobile fractions as revealed by fluorescence recovery after photobleaching. Kymograph and fluorescence recovery after photobleaching analyses demonstrate the transport of intraflagellar transport 25–green fluorescent protein within the developing tail demonstrate no apparent preference for trafficking toward and away from the cell body. The speed of trafficking depends on the stage of sperm development, ranging from highly mobile unrestricted diffusion initially, mobile punctate structures in developing sperm, and immobile punctate structures in mature sperm. Our studies demonstrate that mouse intraflagellar transport 25 travels along the developing sperm flagella in two directions that might be essential for functional sperm formation.
Predictive value of residual active histologic lesions on renal flare in lupus nephritis patients with clinical remission
Authors: Hou Jinhua , Liang Dandan , Quan Songxia , Liu Zhangsuo , Liu Zhihong 
Published: November 2024

ABSTRACT

Background
Renal flare in lupus nephritis (LN) is a crucial contributing factor to poor kidney outcomes. This study aimed at evaluating the predictive value of residual active histologic lesions on renal flare in proliferative LN patients with clinical remission.

Methods
We retrospectively enrolled LN patients with class III/IV ± V (biopsy 1) who had undergone a protocol repeat biopsy (biopsy 2) at 7.3 (IQR: 6.5, 8.4) months after induction therapy with clinical remission and experienced renal flare within 3 years or had been followed up for at least 3 years without renal flare after biopsy 2 with maintenance therapy from two kidney units in China.

Results
A total of 114 eligible patients were included, 28 (24.6%) of whom developed a renal flare. Activity index (AI) at biopsy 2 was significantly associated with LN flare (P &lt; .0001). If AI &gt; 1, the OR for LN flare was 23.1 (95%CI, 5.1–103.8, P &lt; .001). For patients with partial clinical remission compared with those with complete clinical remission, the OR for LN flare was 3.0 (95%CI: 1.1–8.3, P = .029). Multivariate analysis showed that anti-dsDNA positivity, presence of cellular/fibrocellular crescent, and endocapillary hypercellularity at biopsy 2 were independent risk factors for LN flare. When residual active histologic lesions were added to clinical variables, the area under the curve of the prediction model for LN flare significantly increased and the misclassification rate significantly decreased.

Conclusions
Renal flare in LN patients with clinical remission is strongly associated with the residual active histologic lesions.
The sedoheptulose kinase CARKL controls T-cell cytokine outputs and migration by promoting metabolic reprogramming
Authors: Certo Michelangelo , Niven Jennifer , Haas Robert , Rudzinska Paula , Smith Joanne , Cucchi Danilo , Hombrebueno Jose R , Mauro Claudio 
Published: November 2024

Abstract

Background
Immunometabolism is a crucial determinant of immune cell function, influencing cellular activation and differentiation through metabolic pathways. The intricate interplay between metabolism and immune responses is highlighted by the distinct metabolic programs utilized by immune cells to support their functions. Of particular interest is the pentose phosphate pathway (PPP), a key metabolic pathway branching out of glycolysis that plays a pivotal role in generating NADPH and pentose sugars crucial for antioxidant defense and biosynthesis. The sedoheptulose kinase Carbohydrate Kinase-like protein (CARKL), an enzyme involved in the PPP, emerges as a critical regulator of cell metabolism and was previously shown to play a role in macrophage function.

Methods
This study delves into the impact of CARKL expression on T-cell functionality, revealing dynamic alterations in response to cellular activation. Notably, CARKL overexpression leads to significant metabolic shifts in T cells, affecting mitochondrial respiration, ATP production, and inflammatory cytokine profiles. Furthermore, CARKL modulation influences T-cell motility by regulating chemokine receptor expression, particularly compromising CXCR3 expression and impairing T-cell migration in response to specific chemokine signals.

Conclusions
These findings underscore the multifaceted role of CARKL as a metabolic regulator shaping T-cell responses. Overall, our data reveal the complex regulatory mechanisms orchestrated by CARKL in T-cell function, with implications for immune regulation. Further exploration of the molecular interactions between CARKL and metabolic reprogramming in T cells could provide valuable insights into immune regulation and potential therapeutic strategies.
Fertility Beliefs and Outcomes: the Role of Relationship Status and Attractiveness
Authors: Gong Yifan , Skura Tyler , Stinebrickner Ralph , Stinebrickner Todd 
Published: November 2024

Abstract
Unique data from the Berea Panel Study provide new evidence about fertility outcomes before age thirty and beliefs about these outcomes elicited soon after college graduation. Comparing outcomes and beliefs yields a measure of belief accuracy. Individuals who are unmarried and not in relationships at age twenty-four are extremely optimistic about the probability of having children, while married individuals have very accurate beliefs. Novel attractiveness measures are central for understanding fertility beliefs and outcomes for females, but not for males. Marriage is a mechanism that is relevant for understanding differences in beliefs, outcomes and misperceptions across relationship and attractiveness groups.
Support for a ban on characterizing flavours in cigarettes in the UK: a longitudinal online survey
Authors: Moodie Crawford , Best Catherine , Jones Daniel 
Published: November 2024

Abstract
Most European countries have banned flavoured cigarettes. No study has explored whether support for such a ban changes post-implementation. In the UK, a menthol cigarette ban came into force in May 2020. A longitudinal survey in the UK with adult smokers and ex-smokers explored support for the ban in 2019 (N = 3175) and 2022 (N = 3047). Support increased from 2019 (pre-ban) to 2022 (post-ban) for all participants (18.1% to 35.0%), with increased support evident for flavour cigarette smokers (20.7% to 34.5%), non-flavour cigarette smokers (13.5% to 18.1%), and ex-smokers (24.4% to 50.8%). Increased support for tobacco-related policies helps regulators defend policy decisions.
Weak integration allows novel fin shapes and spurs locomotor diversity in reef fishes
Authors: Satterfield Darien R , Yin Bernice , Jung Sky , Hodges-Lisk Samantha , Wainwright Dylan K , Burns Michael D , Wainwright Peter C 
Published: November 2024

Abstract
In functional systems composed of many traits, selection for specialized function can induce trait evolution by acting directly on individual components within the system, or indirectly through networks of trait integration. However, strong integration can also hinder diversification into regions of trait space that are not aligned with axes of covariation among traits. Thus, non-independence among traits may limit functional expansion. We explore this dynamic in the evolution of fin shapes in 106 species from 38 families of coral reef fishes, a polyphyletic assemblage that shows exceptional diversity in locomotor function. Despite expectations of a strong match between form and function, we find subtantial fin shape disparity across species that share a swimming mode. The evolution of fin shape is weakly integrated across the four functionally dominant fins in swimming and integration is weakened as derived swimming modes evolve. The weak integration among fins in the ancestral locomotor condition provides a primary axis of diversification while allowing for off-axis diversification via independent trait responses to selection. However, the evolution of novel locomotor modes coincides with a loss of integration among fins. Our study highlights the need for additional work on the functional consequences of fin shape in fishes.
A first look at the genome structure of hexaploid “Mitcham” peppermint (Mentha × piperita L.)
Authors: Talbot Samuel C , Pandelova Iovanna , Lange Bernd Markus , Vining Kelly J 
Published: November 2024

Abstract
Peppermint, Mentha × piperita L., is a hexaploid (2n = 6x = 72) and the predominant cultivar of commercial mint oil production in the US. This cultivar is threatened because of high susceptibility to the fungal disease verticillium wilt, caused by Verticillium dahliae. This report details the first draft polyploid chromosome-level genome assembly for this mint species. The “Mitcham” genome resource will broaden comparative studies of disease resistance, essential oil biosynthesis, and hybridization events within the genus Mentha. It will also be a valuable contribution to the body of phylogenetic studies involving Mentha and other genera that contain species with varying ploidy levels.
Risk of neurologic events after surgery for mitral valve insufficiency and concomitant Cox-maze IV procedure for atrial fibrillation. A nationwide register-based study
Authors: Albåge Anders , Vanky Farkas , Boano Gabriella , Holmgren Anders , Jidéus Lena , Johansson Birgitta , Kennebäck Göran , Nozohoor Shahab , Scherstén Henrik , Sjögren Johan , Wickbom Anders , Ivert Torbjörn 
Published: November 2024

Abstract

OBJECTIVES
Analysis of the long-term risks of ischaemic stroke and cerebral bleeding in patients with atrial fibrillation after mitral valve surgery and concomitant Cox-maze IV procedure.

METHODS
In total, 397 patients with symptomatic degenerative mitral valve insuffciency and atrial fibrillation, underwent mitral valve surgery and Cox-maze IV in Sweden between 2009 and 2017. In this retrospective nationwide analysis, patients were followed in national patient registers until 30 September 2022.

RESULTS
There were 4 deaths within 30 days (1.0%). Mean follow-up was 8.7 (0.1–13.4) years. Survival without ischaemic stroke or cerebral haemorrhage at 5 and 10 years were 90% and 74%, respectively. Nineteen patients experienced an ischaemic stroke, of which 4 were fatal. Five of 34 patients (14.7%) with a history of stroke preoperatively experienced ischaemic stroke during follow-up. The linearized rate of ischaemic stroke per patient-year was 0.6% and was similar regardless of left atrial appendage closure during surgery or whether a mechanical valve was inserted. The observed ischaemic stroke rate was lower than the predicted rate for all CHA2DS2-VASc score groups. Fourteen patients suffered cerebral bleeding, of which 3 were fatal. Patients who experienced cerebral bleeding were older and had higher mechanical valve implantation rate than those without cerebral bleeding.

CONCLUSIONS
Surgery for mitral valve insufficiency and concomitant Cox-maze IV can be performed with low perioperative risk. There is a low continuing risk of stroke long-term postoperatively that correlates with a higher CHA2DS2-VASc score. Patients with preoperative stroke are at increased risk of postoperative stroke despite atrial fibrillation surgery.
Palovarotene (Sohonos), a synthetic retinoid for reducing new heterotopic ossification in fibrodysplasia ossificans progressiva: history, present, and future
Authors: Hsiao Edward C , Pacifici Maurizio 
Published: November 2024

Abstract
Retinoids are metabolic derivatives of vitamin A and play crucial roles in the regulation of various tissues and organs during prenatal and postnatal development. Active retinoids, like all-trans-retinoic acid, are synthesized in the cytoplasm and subsequently interact with nuclear retinoic acid receptors (RARα, RARβ, and RARγ) to enhance transcription of specific genes. In the absence of retinoids, RARs can still bind to response elements of target genes but repress their transcription. Chondrogenic cell differentiation and cartilage maturation in the growth plate require the absence of retinoid signaling and transcriptional repression by unliganded RARs. This led to the hypothesis that synthetic retinoid agonists may be pharmacological agents to inhibit those cellular processes and counter the excessive formation of cartilage and bone in conditions like heterotopic ossification (HO). HO can be instigated by diverse culprits including trauma, invasive surgeries, inflammatory disorders, or genetic conditions. One such genetic disease is fibrodysplasia ossificans progressiva (FOP), a rare disorder driven by activating mutations in the ACVR1 gene. Patients with FOP have severe and progressive HO formation in soft tissues, leading to extensive permanent loss of mobility and increased mortality. Synthetic retinoid agonists selective for RARα or RARγ showed efficacy against injury-induced and genetic HO in mouse models. The RARγ agonists showed the highest effectiveness, with palovarotene being selected for clinical trials in patients with FOP. Post hoc analyses of phase II and phase III clinical trials showed that palovarotene has significant disease-modifying effects for FOP, but with significant risks such as premature growth plate closure in some younger subjects. This review provides an overview of retinoid and RAR roles in skeletal development and discusses the identification of palovarotene as a potential FOP therapy, the clinical data supporting its regulatory approval in some countries, and the potential applications of this drug for other relevant disorders besides FOP.
CDC73 c.1155-3A&gt;G is a pathogenic variant that causes aberrant splicing, disrupted parafibromin expression, and hyperparathyroidism-jaw tumor syndrome
Authors: Needleman Leor , Chun Nicolette , Sitaraman Sathvika , Tan Marilyn , Sellmeyer Deborah E , Kebebew Electron , Annes Justin P 
Published: November 2024

Abstract
Germline and somatic pathogenic variants in the CDC73 gene, encoding the nuclear protein parafibromin, increase the risk for parathyroid carcinoma and cause hereditary primary hyperparathyroidism (PHPT) syndromes known as familial isolated hyperparathyroidism (FIHP) and hyperparathyroidism-jaw tumor syndrome (HPT-JT). The identification of pathogenic germline variants in PHPT-susceptibility genes can influence surgical planning for parathyroidectomy, guide screening for potential syndromic manifestations, and identify/exonerate at-risk family members. Numerous types of pathogenic germline variants have been described for CDC73-related conditions, including deletion, truncating, missense, and splice site mutations. Here, we report identification of a non-coding germline CDC73 variant (CDC73 c.1155-3A &gt; G), previously categorized as a variant of uncertain significance (VUS), in a family with HPT-JT. This variant, found in two family members with PHPT, altered CDC73 splicing in peripheral blood cells and disrupted parafibromin immunostaining in associated parathyroid adenomas, strongly evidencing its pathogenicity. Sestamibi scintigraphy yielded nondiagnostic localization results for both patients’ parathyroid adenomas, consistent with prior studies suggesting lower sensitivity for small or cystic lesions. Our findings demonstrate key aspects of CDC73-related disorders, highlight the diagnostic value of RNA testing, and exemplify the importance of obtaining a thorough, three-generational family history.
Fracture characteristics of human cortical bone influenced by the duration of in vitro glycation
Authors: Lin Mei-Chun , Sihota Praveer , Kolibová Sofie Dragoun , Fiedler Imke A K , Krug Johannes , Wölfel Eva M , Moritz Manuela , Riedner Maria , Ondruschka Benjamin , Citak Mustafa , Klebig Felix , von Brackel Felix N , Qwamizadeh Mahan , Jähn-Rickert Katharina , Busse Björn 
Published: November 2024

Abstract
Advanced glycation end products (AGEs) accumulate in various tissues, including bone, due to aging and conditions like diabetes mellitus. To investigate the effects of AGEs on bone material quality and biomechanical properties, an in vitro study utilizing human tibial cortex, sectioned into 90 beams, and randomly assigned to three mechanical test groups was performed. Each test group included ribose (c = 0.6 M) treatment at 7-, 14-, and 21-d, alongside control groups (n = 5 per group). Fluorescent AGE (fAGE) and carboxymethyl-lysine (CML) levels were assessed through fluorometric analysis and mass spectrometry, while bone matrix composition was characterized using Fourier-transform infrared and Raman spectroscopy. Mechanical properties were determined through nanoindentation and three-point bending tests on non-notched and notched specimens. The results showed significant increases in fAGEs levels at 7-, 14-, and 21-d compared to controls (119%, 311%, 404%; p = .008, p &lt; .0001, p &lt; .0001, respectively), CML levels also rose substantially compared to controls (383%, 503%, 647%, p &lt; .0001, p &lt; .0001, p &lt; .0001, respectively). Analysis of bone matrix composition showed greater sugars/Amide I ratio at 21-d glycation compared to controls, 7-d, and 14-d (p = .001, .011, .006, respectively); and higher carbonate-to-phosphate ratios in the ribose treatment group compared with controls (p &lt; .05) in the interstitial bone area. Mechanical testing of notched specimens exhibited a higher yield force, pre-yield toughness, and maximum force at 14-d glycation compared to controls and to both 7-d and 21-d glycation (p &lt; .05). Nanoindentation showed that the hardness was lower at 7-d glycation compared to the controls and 21-d glycation (p &lt; .05). In conclusion, the study found altered mechanical properties at 7 and 14 d of glycation, which then returned to control levels at 21 d, indicating a dynamic relationship between glycation duration and mechanical characteristics that deserves further exploration.
Unusual PHEX variants implicate uncommon genetic mechanisms for X-linked hypophosphatemic rickets
Authors: Alzoebie Lama , Li Dong , Wang Xiang , Weber David R , Levine Michael A 
Published: November 2024

Abstract
X-linked hypophosphatemic rickets (XLH), the most common form of hereditary rickets, is characterized by renal phosphate wasting and abnormal vitamin D metabolism due to elevated circulating levels of the phosphatonin fibroblast growth factor 23 (FGF23). Dominant inactivating variants of the phosphate regulating endopeptidase homolog, X-linked (PHEX), gene are present in patients with XLH, and more than half of affected patients carry de novo variants. We report on 3 families in whom affected members had highly unusual PHEX pathogenic variants. In 1 family we identified a previously described deep intronic PHEX variant (c.1768 + 173A&gt;G) in the proband and her affected son. This variant is also near a previously reported PHEX variant (c.1768 + 177_1768 + 180dupGTAA) and is predicted to affect splicing by SpliceAI (delta score: 0.95) through creation of a new donor splice site. In a second proband we identified 2 pathogenic de novo and novel PHEX variants, c.2083delT (p.Ser695Profs*45) and c.2085delC (p.Tyr696Thrfs*44), that were present on different alleles, consistent with mosaicism for 3 PHEX alleles. The third proband also carried 2 PHEX variants (c.755 T&gt;C [p.Phe252Ser] and c.759G&gt;A [p.Met253Ile]), but in this case both variants were present on the same PHEX allele. These studies expand the molecular catalog of pathogenic PHEX variants in XLH and emphasize the importance of deep intronic sequencing and comprehensive family studies. Conventional approaches to genetic diagnosis may not be adequate to identify or characterize the disease-causing variants in the PHEX gene in some patients with likely XLH.
Elastic frequency controllable envelope inversion
Authors: Du Qiu , Gao Zhaoqi , Gao Jinghuai 
Published: November 2024

Abstract
Although elastic full waveform inversion is considered a high-resolution seismic inversion method, it is sensitive to the initial model. When the initial model lacks long-wavelength components, the inversion results may be inaccurate. This limitation frequently results in cycle-skipping during the inversion process. Elastic envelope inversion (EEI) is an effective way to build initial models as input for EFWI. However, EEI ignores the difference in sensitivity of different frequency data to the cycle-skipping problem, which limits its performance. This paper introduces the elastic frequency controllable envelope (EFCE), a novel type of envelope with frequency-selection characteristics tailored for elastic data. Moreover, to enhance the utilization of weak reflected information, a modified version of EFCE named residual-modification-aided EFCE (RMAEFCE) is proposed. Building on RMAEFCE, we define a novel objective function and subsequently propose an innovative EFWI approach called RMAEFCE inversion (RMAEFCEI), with the aim of building accurate long-wavelength velocity models that include both P-wave and S-wave. Numerical experiments carried out using the Marmousi model show that our approach markedly outperforms EEI, effectively mitigating the cycle-skipping issue. When employing the initial models established by RMAEFCEI, EFWI can output satisfactory final models. In addition, RMAEFCEI can build acceptable long-wavelength velocity models even with an inaccurate wavelet, indicating that it is more robust to wavelet error.