bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cow’s Milk-Related Symptom Score (CoMiSS): From Bristol to Brussels Stool Scale
Authors: Bajerova Katerina , Salvatore Silvia , Dupont Christophe , Kuitunen Mikael , Meyer Rosan , Ribes-Koninckx Carmen , Shamir Raanan , Szajewska Hania , Staiano Annamaria , Vandenplas Yvan 
Published: September 2023

Objectives:
The Cow’s Milk-related Symptom Score (CoMISS) is an awareness tool for evaluating cow’s milk-related symptoms in otherwise healthy infants <1 year of age. This study assessed whether replacing the Bristol Stool Form Scale (BSFS) with the Brussels Infants and Toddlers Stool Scale (BITSS) in non-toilet-trained infants would modify the overall CoMiSS and change the clinical approach regarding potential cow’s milk allergy.

Methods:
Non-toilet-trained infants aged <13 months were assessed by CoMiSS using the 7 images from the BSFS (CoMiSS-BSFS) compared to the 4 images of stools from BITSS (CoMiSS-BITSS). The Wilcoxon signed-rank test and Pearson correlation coefficient were calculated. A post hoc analysis using identical tests was performed in subsets of CoMiSS-BSFS scores ≥10, ≥12, ≤5, and ≥6.

Results:
Eight hundred forty-four pairwise scores were collected. Applying the Wilcoxon test over the complete dataset, the difference between CoMiSS-BSFS and CoMiSS-BITSS was statistically significant (P < 0.001). However, there was no significant difference in the subsets with CoMiSS-BSFS ≥10, ≥12, and ≥6 (P = 0.84, P = 0.48, and P = 0.81, respectively). The significant difference remained restricted to the group with CoMiSS-BSFS ≤5, considered at low risk for CM-related symptoms (P < 0.001).

Conclusion:
Replacing BSFS with BITSS does not change the cutoff for awareness of possible CM-related symptoms and will not impact the use of CoMiSS in clinical practice. Changes in CoMiSS remained limited to the subgroup with a low risk for CM-related symptoms.
Hypoxia-inducible Factor-1α and mTOR as a Potential Therapeutic Target in Endometriosis: An Immunohistochemical Study
Authors: Badary Dalia M. , Abou-Taleb Hisham A. , Ibrahim Maha 
Published: September 2023

Background and Study Aim:
We aim to study the immunohistochemical expression of both hypoxia-inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR) in endometriosis to provide new evidence for a targeted endometriosis therapy.

Patients and Methods:
This study comprised 106 endometriotic cases diagnosed clinically and histopathologically. The immunohistochemical method was done to determine the expression of HIF-1α and mTOR

Results:
Endometriotic glands showed significant cytoplasmic expression of both markers in patients with poor ovulation, severe endometriosis, and infertile for >2 years (P<0.001). Also, patients with intense and worst pain show significant immunohistochemical expression of both markers (P<0.001). There is a significant correlation between mTOR and HIF-1α expression in endometriotic tissue samples as P<0.001.

Conclusions:
Our data suggest that both mTOR and its downstream target HIF-1α transcription factor are both disrupted in patients with endometriosis, which is consistent with aberrant activation of these pathways and their possible contribution to the pathogenesis of endometriosis. These results could offer a promising novel opportunity to be blocked therapeutically. As new management options need to be refined in particular in severe cases and infertile patients with endometriosis, therefore future studies are warranted to investigate treating endometriosis with mTOR inhibitors; the latter are already in clinical trials in phase III and IV, treating solid tumors as well as non-neoplastic disorders.
Extraovarian Dysgerminoma Involving the Uterine Cervix: A Rare Case Report With Literature Review
Authors: Yoshino Yasunori , Yanai Shiori , Sawada Mari , Sakate Shintaro , Kanno Kiyoshi , Hada Tomonori , Ueda Toshihiro , Tabata Tetsuya , Omori Masako , Andou Masaaki 
Published: September 2023

Primary extraovarian dysgerminoma (EOD) is a very rare disease. There is no literature about primary EOD involving the uterine cervix. We herein present details of a unique case of primary EOD involving the uterine cervix. A 46-year-old woman with uterine cervical tumor was referred to our institution with atypical genital bleeding. A polypoid tumor localized to the uterine cervix was found. Cervical biopsy detected malignant components of likely nonepithelial cell origin. Preoperative imaging examinations showed a uterine cervical tumor measuring ~5 cm, suggestive of malignancy without distant or lymph node metastases. The patient underwent abdominal radical hysterectomy with pelvic lymph node dissection according to the standard treatment for stage IB3 cervical cancers. The pathological diagnosis was dysgerminoma involving the uterine cervix and the right fallopian tube. Immunohistochemical results were as follows: SALL4 (+), octamer-binding transcription factor 4 (+), D2-40 (+), and c-Kit (+). She received 3 cycles of adjuvant chemotherapy with bleomycin, etoposide, and cisplatin. The disease did not recur up to 14 months after surgery. This is the first-ever published case of primary EOD involving the uterine cervix among previously reported EOD cases. Reported cases of EOD in female genital tract are also reviewed. Our case provides more extensive insights for pathologists to consider the differential diagnosis of cervical lesions. In our case, combination therapy involving a surgical approach—according to cervical cancers and adjuvant chemotherapy as used for ovarian dysgerminomas—was effective. Future verification is needed regarding the best approach for treating uterine cervical dysgerminomas.
Effects of Orbicularis Oculi Flap Suspension on Transcutaneous Lower Blepharoplasty
Authors: Lee Hyunkyu , Shin Hyemi , Baek Sehyun 
Published: September 2023

Objective:
The purpose of this study was to analyze the clinical effects of orbicularis oculi muscle suspension in conjunction with transcutaneous blepharoplasty in patients 60 years of age or older.

Methods:
A retrospective study was conducted on patients aged 60 or older who underwent orbicularis oculi flap suspension in conjunction with transcutaneous blepharoplasty to treat lower lid festoons, lower lid fat prolapse, and lid laxity at Korea University Guro Hospital. The outcomes were surgical success rate, recurrence rate, postoperative complications, and patient satisfaction.

Results:
In total, 39 patients (18 males and 21 females) were included, with an average age of 67.5 years (60–86 y) and a follow-up period of 145.7 days (95–195 d). In all patients, eyelid laxity was effectively corrected, and there was no recurrence of eyelid laxity after surgery. Three patients suffered postoperative complications, transient skin edema in 2 patients, and transient ectropion in 1 patient. Subjective satisfaction score following surgery was high, with an average score of 2.56 out of 3 points.

Conclusions:
Orbicularis oculi flap suspension with transcutaneous blepharoplasty can shorten operation time due to surgical ease. It also has the advantage of not involving conjunctival-related complications such as conjunctival edema since it does not pass through the conjunctiva. Finally, it can successfully treat lid laxity and could be used in lower blepharoplasty procedures.
How Does Omitting Additional Surgery after Local Excision Affect the Prognostic Outcome of Patients with High-risk T1 Colorectal Cancer?
Authors: Ouchi Akira , Komori Koji , Masahiro Tajika , Toriyama Kazuhiro , Kajiwara Yoshiki , Oka Shiro , Fukunaga Yosuke , Hotta Kinichi , Ikematsu Hiroaki , Tsukamoto Shunsuke , Nagata Shinji , Yamada Kazutaka , Konno Maki , Ishihara Soichiro , Saitoh Yusuke , Matsuda Kenji , Togashi Kazutomo , Ishiguro Megumi , Kuwai Toshio , Okuyama Takashi , Ohuchi Akihiro , Ohnuma Shinobu , Sakamoto Kazuhiro , Sugai Tamotsu , Katsumata Kenji , Matsushita Hiro-o , Nakai Keisuke , Uraoka Toshio , Akimoto Naohiko , Kobayashi Hirotoshi , Ajioka Yoichi , Sugihara Kenichi , Ueno Hideki ,   on behalf of the Study Group for the JSCCR-T study
Published: September 2023

Objective:
To investigate how omitting additional surgery after local excision (LE) affects patient outcomes in high-risk T1 colorectal cancer (CRC).

Summary Background Data:
It is debatable whether additional surgery should be performed for all patients with high-risk T1 CRC regardless of the tolerability of invasive procedures.

Methods:
Patients who had received LE for T1 CRC at the Japanese Society for Cancer of the Colon and Rectum (JSCCR) institutions between 2009 and 2016 were analyzed. Those who had received additional surgical resection and who did not were matched one-on-one by the propensity score (PS)-matching method. A total of 401 PS-matched pairs were extracted from 1,975 patients at 27 JSCCR institutions and compared.

Results:
Regional lymph node metastasis was observed in 31 (7.7%) patients in the LE+surgery group. Comparatively, the incidence of oncologic adverse events was low in the LE-alone group, such as the 5-year cumulative risk of local recurrence (4.1%) or overall recurrence (5.5%). In addition, the difference in the 5-year CSS between the LE+surgery and LE-alone groups was only 1.8% (99.7% and 97.9%, respectively), whereas the 5-year OS was significantly lower in the LE-alone group than in the LE+surgery group (88.5% vs. 94.5%, respectively (P=0.002).

Conclusions:
Those who had been decided to omit additional surgery at the dedicated center for CRC treatment presented a small number of oncologic events and a satisfactory CSS, which may suggest an important role of risk assessment regarding non-oncologic adverse events to achieve a best practice for each individual with high-risk T1 tumors.
Efficacy of Standardized Process Management of Early Postoperative Enteral Nutrition After Laparoscopic Hepatectomy: A Randomized Controlled Trial
Authors: Gao Yun , Wang Fang 
Published: September 2023

Background:
We sought to investigate the efficacy of standardized process management of early postoperative enteral nutrition in patients undergoing laparoscopic hepatectomy.

Methods:
From January 2022 to January 2023, a total of 98 patients undergoing laparoscopic hepatectomy in our hospital were enrolled in this prospective study. The participants were allocated into the study group (49 cases, given standardized process management of early postoperative enteral nutrition) and the control group (49 cases, given conventional early postoperative enteral nutrition) based on a random number table. Observation indicators included postoperative recovery, nutritional status, quality of life, and complications.

Results:
The time of first anal exhaust, eating, off-bed, first defecation, and postoperative hospital stay in the 2 groups was significantly shorter than those in the control group (P<0.05). After the intervention, the levels of transferrin, prealbumin, and albumin in the study group were evidently higher than those in the control group (P<0.05). The scores of overall health, body pain, body function, physiological function, vitality, social function, emotional function, and mental health in the study group were significantly higher than those in the control group after intervention (P<0.05).

Conclusions:
The standardized process management of early postoperative enteral nutrition showed promising results in effectively improving the nutritional status, rehabilitation, and quality of life, as well as reducing the incidence of related complications among patients undergoing laparoscopic hepatectomy, which supports a wide application in clinical practice.
Cellular taxonomy of the preleukemic bone marrow niche of acute myeloid leukemia
Authors: Goda Chinmayee , Kulkarni Rohan , Rudich Alexander , Karunasiri Malith , Balcioglu Ozlen , Al-Marrawi Yzen , Korn Erin , Kanna Sanjay , Garfinkle Elizabeth A.R. , Mundy-Bosse Bethany , Zhang Bin , Marcucci Guido , Mardis Elaine R , Garzon Ramiro , Miller Katherine E , Dorrance Adrienne M 
Published: September 2023

ABSTRACTMutations in hematopoietic stem/progenitor cells (HSPCs) can remain dormant within the bone marrow (BM) for decades before leukemia onset. Understanding the mechanisms by which these mutant clones eventually slead to full blown leukemia is of critical importance to develop strategies to eliminate these clones before they achieve their full leukemogenic potential. Recent data suggest that leukemic stem cells (LSCs) induce alterations within BM microenvironment (BMM) favoring LSC growth over normal HSCs. However, the cross talk between preleukemic stem cells (pLSC) and BMM is not completely understood. We hypothesize that pLSC induces critical changes within the BMM that are critical for leukemogenesis. To address this question, we are using our previously developed murine model of AML that highly recapitulates the human disease, develops AML sporadically with a preleukemic phase in which mice display normal white blood counts (WBCs) and absence of blasts in the BM. Thus, this is an excellent model to evaluate changes in the BMM that occurs during progression into AML. Using this model we performed single cell RNA-sequencing on cells from the BMM compared to wild-type (WT) controls. Overall, we defined the transcriptional profiles of pre-leukemic BMM cells and observed decreased percentages of normal BMM cells such as LepR+ mesenchymal stem cells (MSCs) and endothelial cells (ECs), known to regulate normal HSC function. Concomitantly, we found increases in CD55+ fibroblasts and NG2+ pericytes, that might play a more important role in regulation of pre-LSCs. Preleukemic CD55+ fibroblasts had a higher proliferation rate and showed significant down-regulation of several collagen genes known for regulating extra cellular matrix (ECM) including:Col1a1, Col1a2, Col3a1, Col4a1, andCol6a1,suggesting that ECM remodeling occurs in the early stages of leukemogenesis. Importantly, co-culture assays found that pre-leukemic CD55+ BM fibroblasts expanded pre-LSCs significantly over normal HSCs. In conclusion, we have identified distinct changes in the preleukemic BMM and identified a novel CD55+ fibroblast population that is expanded in preleukemic BMM that promote the fitness of pre-LSCs over normal HSCs.STATEMENT OF SIGNIFICANCEWe have identified changes in the BMM landscape that define a preleukemic BM niche which includes the expansion of a novel CD55+ fibroblast population. These data suggest that a distinct preleukemic BM niche exists and preferentially supports LSC survival and expansion over normal HSCs to promote leukemogenesis.
An engineered tumor organoid model reveals cellular identity and signaling trajectories underlying translocation RCC
Authors: Ganpat Maroussia M.P. , Morales-Rodriguez Francisco , Pham Nhung , Lijnzaad Philip , de Souza Terezinha , Derakshan Sepide , Fumagalli Arianna , Zeller Peter , Balwierz Aleksandra , Ayyildiz Dilara , van den Heuvel-Eibrink Marry M. , de Krijger Ronald R. , van Oudenaarden Alexander , Margaritis Thanasis , de Sousa Lopes Susana M. Chuva , Drost Jarno 
Published: September 2023

AbstractTranslocation renal cell carcinoma (tRCC) is a rare, aggressive type of kidney cancer primarily occurring in children. They are genetically defined by translocations involving MiT/TFE gene family members, TFE3 or, in rare cases, TFEB. The biology underlying tRCC development remains poorly understood, partly due to the lack of representative experimental models. Here, we utilized human kidney organoids, or tubuloids, to engineer a tRCC model by expression of one of the most common MiT/TFE fusions, SFPQ-TFE3. Fusion expressing tubuloids adopt a tRCC-like phenotype and gene expression signaturein vitroand grow as clear cell RCC upon xenotransplantation in mice. Genome-wide binding analysis reveals that SFPQ-TFE3 reprograms gene expression signatures by aberrant, gain-of-function genome-wide DNA binding. Combining these analyses with single-cell mRNA readouts reveals an epithelium-to-mesenchymal differentiation trajectory underlying tRCC transformation, potentially caused by deregulated Wnt signaling. Our study demonstrates that SFPQ-TFE3 expression is sufficient to transform kidney epithelial cells into tRCC and defines the trajectories underlying malignant transformation, thereby facilitating the development of new therapeutic interventions.
Neural circuit models for evidence accumulation through choice-selective sequences
Authors: Brown Lindsey S. , Cho Jounhong Ryan , Bolkan Scott S. , Nieh Edward H. , Schottdorf Manuel , Tank David W. , Brody Carlos D. , Witten Ilana B. , Goldman Mark S. 
Published: September 2023

ABSTRACTDecision making is traditionally thought to be mediated by populations of neurons whose firing rates persistently accumulate evidence across time. However, recent decision-making experiments in rodents have observed neurons across the brain that fire sequentially as a function of spatial position or time, rather than persistently, with the subset of neurons in the sequence depending on the animal’s choice. We develop two new candidate circuit models, in which evidence is encoded either in the relative firing rates of two competing chains of neurons or in the network location of a stereotyped pattern (“bump”) of neural activity. Encoded evidence is then faithfully transferred between neuronal populations representing different positions or times. Neural recordings from four different brain regions during a decision-making task showed that, during the evidence accumulation period, different brain regions displayed tuning curves consistent with different candidate models for evidence accumulation. This work provides mechanistic models and potential neural substrates for how graded-value information may be precisely accumulated within and transferred between neural populations, a set of computations fundamental to many cognitive operations.
Permanent Neonatal diabetes-causing Insulin mutations have dominant negative effects on beta cell identity
Authors: Zhang Yuwei , Sui Lina , Du Qian , Haataja Leena , Yin Yishu , Viola Ryan , Xu Shuangyi , Nielsson Christian Ulrik , Leibel Rudolph L. , Barbetti Fabrizio , Arvan Peter , Egli Dieter 
Published: September 2023

AbstractHeterozygous coding sequence mutations of theINSgene are a cause of permanent neonatal diabetes (PNDM) that results from beta cell failure. We explored the causes of beta cell failure in two PNDM patients with two distinctINSmutations. Using b and mutated hESCs, we detected accumulation of misfolded proinsulin and impaired proinsulin processingin vitro, and a dominant-negative effect of these mutations on the in vivo performance of patient-derived SC-beta cells after transplantation into NSG mice. These insulin mutations derange endoplasmic reticulum (ER) homeostasis, and result in the loss of beta-cell mass and function. In addition to anticipated apoptosis, we found evidence of beta-cell dedifferentiation, characterized by an increase of cells expressing both Nkx6.1 and ALDH1A3, but negative for insulin and glucagon. These results highlight both known and novel mechanisms contributing to the loss and functional failure of human beta cells with specific insulin gene mutations.
WITHDRAWN: Demographic and ecological drivers of infectome diversity in companion cats
Authors: Sun Yankuo , Xing Jiabao , Xu Sijia , Li Yue , Gao Han , Cheng Song , Kuang Qiyuan , Dong Jun , Zhang Tianyou , Lu Gang , Baele Guy , Zhang Guihong 
Published: September 2023

Withdrawal StatementThe authors have withdrawn their manuscript owing to data ambiguity. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Visual cortical area contributions to the transient, multifocal and steady-state VEP: A forward model-informed analysis
Authors: Mohr Kieran S , Geuzebroek Anna C , Kelly Simon P 
Published: September 2023

AbstractCentral to our understanding of how visual evoked potentials (VEPs) contribute to visual processing is the question of where their anatomical sources are. Three well-established measures of low-level visual cortical activity are widely used: the first component (“C1”) of the transient and multifocal VEP, and the steady-state VEP (SSVEP). Although primary visual cortex (V1) activity has often been implicated in the generation of all three signals, their dominant sources remain uncertain due to the limited resolution and methodological heterogeneity of source modelling. Here, we provide the first characterisation of all three signals in one analytic framework centred on the ‘cruciform model’, which describes how scalp topographies of V1 activity vary with stimulus location due to the retinotopy and unique folding pattern of V1. We measured the transient C1, multifocal C1, and SSVEPs driven by an 18.75Hz and 7.5Hz flicker, and regressed them against forward-models of areas V1, V2 and V3 generated from the Benson-2014 retinotopy atlas. The topographic variations of all four VEP signals across the visual field were better captured by V1 models, explaining between 2-6 times more variance than V2/V3. Models with all three visual areas improved fit further, but complementary analyses of temporal dynamics across all three signals indicated that the bulk of extrastriate contributions occur considerably later than V1. Overall, our data support the use of peak C1 amplitude and SSVEPs to probe V1 activity, although the SSVEP contains stronger extrastriate contributions. Moreover, we provide elaborated heuristics to distinguish visual areas in VEP data based on signal lateralization as well as polarity inversion.
A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria
Authors: Faniyan Tumininu S. , Zhang Xinyi , Morgan Donald A. , Robles Jorge , Bathina Siresha , Brookes Paul S. , Rahmouni Kamal , Perry Rachel J. , Chhabra Kavaljit H. 
Published: September 2023

AbstractThe kidneys facilitate energy conservation through reabsorption of nutrients including glucose. Almost all the filtered blood glucose is reabsorbed by the kidneys. Loss of glucose in urine (glycosuria) is offset by an increase in endogenous glucose production to maintain normal energy supply in the body. How the body senses this glucose loss and consequently enhances glucose production is unclear. Using renalGlut2knockout mice, we demonstrate that elevated glycosuria activates the hypothalamic-pituitary-adrenal axis, which in turn drives endogenous glucose production. This phenotype was attenuated by selective afferent renal denervation, indicating the involvement of the afferent nerves in promoting the compensatory increase in glucose production. In addition, through plasma proteomics analyses we observed that acute phase proteins - which are usually involved in body’s defense mechanisms against a threat – were the top candidates which were either upregulated or downregulated in renalGlut2KO mice. Overall, afferent renal nerves contribute to promoting endogenous glucose production in response to elevated glycosuria and loss of glucose in urine is sensed as a biological threat in mice. These findings may be useful in improving efficiency of drugs like SGLT2 inhibitors that are intended to treat hyperglycemia by enhancing glycosuria but are met with a compensatory increase in endogenous glucose production.