bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicentric Carpo-Tarsal Osteolysis Syndrome (MCTO) and “Function Profile”: a rehabilitative approach
Authors: Ronchetti Anna Bruna , Usai Marina , Savino Valentina , Scaglione Marco , Tacchino Chiara Maria , Bertamino Marta , Moretti Paolo , Di Rocco Maja 
Published: December 2023

Abstract
Background
Multicentric Carpo-Tarsal Osteolysis Syndrome (MCTO) is an autosomal dominant disease with increased bone reabsorption in the carpus and tarsus and the elbows, knees and spine. The disease is extremely heterogeneous and secondary and tertiary injuries vary widely and can lead to progressive disability and severe functional limitations. In addition to the available and upcoming drug therapies, physical medicine and rehabilitation are important treatment options. Currently, the indication and plan are overlooked, nonspecific and reported only for one patient.

Methods
We describe a case series of MCTO patients diagnosed and followed by a centre to identify functional deficit as a potential clinical marker of disease progression for future etiological therapies. In addition, we define a symptomatic treatment approach and specific clinical management, including a patient-centred rehabilitation approach. Functional assessments are performed independently by a multidisciplinary group to establish the functional abilities of patients and the relationship between residual motor skills and their degree of autonomy and participation. We suggest a way to identify a rehabilitation plan based on a specific disease using the International Classification of Functioning, Disability and Health Children and Youth (ICF-CY).

Results
To define a reliable and reproducible “Function Profile”, through age and over time, we used to value the disease status according to the ICF-CY domains. It could be used to determine the complexity of the illness, its overall impact on the complexity of the person and the burden on the caregiver, and an eventual short- and long-term rehabilitation plan for MCTO and other ultra-rare diseases.

Conclusion
Based on the MCTO experience, we suggest a way to determine a rehabilitation plan based on a specific disease and patient needs, keeping in mind that often the final point is not recovering the full function but improving or maintaining the starting point. In all cases, each patient at the time of diagnosis requires a functional assessment that must be repeated over time to adjust the course of rehabilitation. The evaluations revealed the importance of early rehabilitation management in enhancing independence, participation and control of stress deconditioning, shrinking of muscle tendons and loss of movement to immobility.
Transcription factors in fibroblast plasticity and CAF heterogeneity
Authors: Melchionna Roberta , Trono Paola , Di Carlo Anna , Di Modugno Francesca , Nisticò Paola 
Published: December 2023

AbstractIn recent years, research focused on the multifaceted landscape and functions of cancer-associated fibroblasts (CAFs) aimed to reveal their heterogeneity and identify commonalities across diverse tumors for more effective therapeutic targeting of pro-tumoral stromal microenvironment. However, a unified functional categorization of CAF subsets remains elusive, posing challenges for the development of targeted CAF therapies in clinical settings.The CAF phenotype arises from a complex interplay of signals within the tumor microenvironment, where transcription factors serve as central mediators of various cellular pathways. Recent advances in single-cell RNA sequencing technology have emphasized the role of transcription factors in the conversion of normal fibroblasts to distinct CAF subtypes across various cancer types.This review provides a comprehensive overview of the specific roles of transcription factor networks in shaping CAF heterogeneity, plasticity, and functionality. Beginning with their influence on fibroblast homeostasis and reprogramming during wound healing and fibrosis, it delves into the emerging insights into transcription factor regulatory networks. Understanding these mechanisms not only enables a more precise characterization of CAF subsets but also sheds light on the early regulatory processes governing CAF heterogeneity and functionality. Ultimately, this knowledge may unveil novel therapeutic targets for cancer treatment, addressing the existing challenges of stromal-targeted therapies.
Update on the INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4): progress and baseline features in 2053 participants
Authors: Chen Chen , Lin Yapeng , Liu Feifeng , Chen Xiaoying , Billot Laurent , Li Qiang , Guo Yiija , Liu Hueiming , Si Lei , Ouyang Menglu , Zhang Chunfang , Arima Hisatomi , Bath Philip M. , Ford Gary A. , Robinson Thompson , Sandset Else Charlotte , Saver Jeffrey L. , Sprigg Nikola , van der Worp H. Bart , Liu Gang , Song Lili , Yang Jie , Li Gang , Anderson Craig S. ,   for the INTERACT4 Investigators
Published: December 2023

Abstract
Background and aims
Uncertainty persists over the effects of blood pressure (BP) lowering in acute stroke. The INTEnsive ambulance-delivered blood pressure Reduction in hyper-Acute stroke Trial (INTERACT4) aims to determine efficacy and safety of hyperacute intensive BP lowering in patients with suspected acute stroke. Given concerns over the safety of this treatment in the pre-hospital setting, particularly in relation to patients with intracerebral hemorrhage, we provide an update on progress of the study and profile of participants to date.

Methods
INTERACT4 is an ongoing multicentre, ambulance-delivered, randomized, open-label, blinded endpoint trial of pre-hospital BP lowering in patients with suspected acute stroke and elevated BP in China. Patients are randomized via a mobile phone digital system to intensive (target systolic BP [SBP] <140mmHg within 30 min) or guideline-recommended BP management. Primary outcome is an ordinal analysis of the full range of scores on the modified Rankin scale scores at 90 days.

Results
Between March 2020 and April 2023, 2053 patients (mean age 70 years, female 39%) were recruited with a mean BP 178/98 mmHg in whom 45% have a diagnosis of primary intracerebral hemorrhage upon arrival at hospital. At the time of presentation to hospital, the mean SBP was 160 and 170mmHg in the intensive and control groups (Δ10 mmHg), respectively. The independent data and safety monitoring board has not identified any safety concerns and recommended continuation of the trial. The sample size was reduced from 3116 to 2320 after meetings in August 2022 as the stroke mimic rate was persistently lower than initially estimated (6% vs 30%). The study is expected to be completed in late 2023 and the results announced in May 2024.

Conclusions
INTERACT4 is on track to provide reliable evidence of the effectiveness of ambulance-delivered intensive BP lowering in patients with suspected acute stroke.

Trial registration
ClinicalTrials.gov NCT03790800; registered on 2 January 2019. Chinese Trial Registry ChCTR1900020534, registered on 7 January 2019.
Identification of isothiazolones analogues as potent bactericidal agents against antibiotic resistant CRE and MRSA strains
Authors: Jin Wenbin , Xu Chen , Dong Ning , Chen Kaichao , Zhang Die , Ning Jinhua , Li Yunbing , Zhang Guangfen , Ke Jin , Hou Anguo , Chen Linyun , Chen Sheng , Chan Kin-Fai 
Published: December 2023

AbstractCarbapenem-resistant Enterobacterales (CRE) has emerged as a worldwide spread nosocomial superbug exhibiting antimicrobial resistance (AMR) to all current antibiotics, leaving limited options for treating its infection. To discovery novel antibiotics against CRE, we designed and synthesized a series of 14 isothiazol-3(2H)-one analogues subjected to antibacterial activity evaluation against Escherichia coli (E. coli) BL21 (NDM-1) and clinical strain E. coli HN88 for investigating their structure–activity relationships (SAR). The results suggested that 5-chloroisothiazolone core with an N-(4-chlorophenyl) substitution 5a was the most potent antibacterial activity against the E. coli BL21 (NDM-1) with MIC value of less than 0.032 μg/mL, which was at least 8000-fold higher than the positive control Meropenem (MRM). It also displayed 2048-fold potent than the positive control MRM against E. coli HN88. Additionally, SAR analysis supported the conclusion that compounds with a chloro-group substituted on the 5-position of the heterocyclic ring was much more potent than other positions. The board spectrum analysis suggested that compound 5a showed a promising antimicrobial activity on MRSA and CRE pathogens. Meanwhile, cytotoxicity study of compound 5a suggested that it had a therapeutic index value of 875, suggesting future therapeutic potential. In vivo efficacy study declared that compound 5a could also protect the BALB/c mice against American type culture collection (ATCC) 43,300. Further screening of our compounds against a collection of CRE strains isolated from patients indicated that compound 5 g displayed much stronger antibacterial activity compared with MRM. In conclusion, our studies indicated that isothiazolones analogues could be potent bactericidal agents against CRE and MRSA pathogens.
First report of cutaneous leishmaniasis caused by Leishmania donovani in Ethiopia
Authors: Amare Gashaw Azanaw , Mekonnen Gebeyaw Getnet , Kassa Mekibib , Addisu Ayenew , Kendie Desalegn Adane , Tegegne Banchamlak , Abera Adugna , Tadesse Dagimawie , Getahun Seid , Wondmagegn Yenesew Mihret , Merdekios Behailu , Asres Mezgebu Silamsaw , van Griensven Johan , Van der Auwera Gert , van Henten Saskia , Pareyn Myrthe 
Published: December 2023

Abstract
Background
Leishmaniasis is a common neglected tropical disease in Ethiopia. Visceral leishmaniasis (VL) caused by Leishmania donovani presents in the lowlands, while cutaneous leishmaniasis (CL) affects people living in the highlands. Although CL is described as being caused by Leishmania aethiopica, there is also evidence of L. tropica and L. major isolated from a patient, sand flies and potential reservoirs. Information on species causing CL in Ethiopia is patchy, and no nation-wide study has ever been done. Understanding which species are causing CL in Ethiopia can have important implications for patient management and disease prevention.

Methods
We analyzed stored routine samples and biobanked DNA isolates from previously conducted studies of CL patients from different centers in the north, center and south of Ethiopia. Species typing was performed using ITS-1 PCR with high-resolution melt (HRM) analysis, followed by HSP70 amplicon sequencing on a selection of the samples. Additionally, sociodemographic, clinical and laboratory data of patients were analyzed.

Results
Of the 226 CL samples collected, the Leishmania species could be determined for 105 (45.5%). Leishmania aethiopica was identified in 101 (96.2%) samples from across the country. In four samples originating from Amhara region, northwestern Ethiopia, L. donovani was identified by ITS-1 HRM PCR, of which two were confirmed with HSP70 sequences. While none of these four patients had symptoms of VL, two originated from known VL endemic areas.

Conclusions
The majority of CL was caused by L. aethiopica, but CL due to L. tropica and L. major cannot be ruled out. Our study is the first to our knowledge to demonstrate CL patients caused by L. donovani in Ethiopia. This should spark future research to investigate where, how and to which extent such transmission takes place, how it differs genetically from L. donovani causing VL and whether such patients can be diagnosed and treated successfully with the currently available tools and drugs.

Graphical Abstract
Deep learning predicts cervical lymph node metastasis in clinically node-negative papillary thyroid carcinoma
Authors: Zhou Li-Qiang , Zeng Shu-E. , Xu Jian-Wei , Lv Wen-Zhi , Mei Dong , Tu Jia-Jun , Jiang Fan , Cui Xin-Wu , Dietrich Christoph F. 
Published: December 2023

Abstract
Objectives
Precise determination of cervical lymph node metastasis (CLNM) involvement in patients with early-stage thyroid cancer is fairly significant for identifying appropriate cervical treatment options. However, it is almost impossible to directly judge lymph node metastasis based on the imaging information of early-stage thyroid cancer patients with clinically negative lymph nodes.

Methods
Preoperative US images (BMUS and CDFI) of 1031 clinically node negative PTC patients definitively diagnosed on pathology from two independent hospitals were divided into training set, validation set, internal test set, and external test set. An ensemble deep learning model based on ResNet-50 was built integrating clinical variables, BMUS, and CDFI images using a bagging classifier to predict metastasis of CLN. The final ensemble model performance was compared with expert interpretation.

Results
The ensemble deep convolutional neural network (DCNN) achieved high performance in predicting CLNM in the test sets examined, with area under the curve values of 0.86 (95% CI 0.78–0.94) for the internal test set and 0.77 (95% CI 0.68–0.87) for the external test set. Compared to all radiologists averaged, the ensemble DCNN model also exhibited improved performance in making predictions. For the external validation set, accuracy was 0.72 versus 0.59 (p = 0.074), sensitivity was 0.75 versus 0.58 (p = 0.039), and specificity was 0.69 versus 0.60 (p = 0.078).

Conclusions
Deep learning can non-invasive predict CLNM for clinically node-negative PTC using conventional US imaging of thyroid cancer nodules and clinical variables in a multi-institutional dataset with superior accuracy, sensitivity, and specificity comparable to experts.

Critical relevance statement
Deep learning efficiently predicts CLNM for clinically node-negative PTC based on US images and clinical variables in an advantageous manner.

Key points
• A deep learning-based ensemble algorithm for predicting CLNM in PTC was developed.
• Ultrasound AI analysis combined with clinical data has advantages in predicting CLNM.
• Compared to all experts averaged, the DCNN model achieved higher test performance.

Graphical Abstract
Predicting tumor deposits in rectal cancer: a combined deep learning model using T2-MR imaging and clinical features
Authors: Jin Yumei , Yin Hongkun , Zhang Huiling , Wang Yewu , Liu Shengmei , Yang Ling , Song Bin 
Published: December 2023

Abstract
Background
Tumor deposits (TDs) are associated with poor prognosis in rectal cancer (RC). This study aims to develop and validate a deep learning (DL) model incorporating T2-MR image and clinical factors for the preoperative prediction of TDs in RC patients.

Methods and methods
A total of 327 RC patients with pathologically confirmed TDs status from January 2016 to December 2019 were retrospectively recruited, and the T2-MR images and clinical variables were collected. Patients were randomly split into a development dataset (n = 246) and an independent testing dataset (n = 81). A single-channel DL model, a multi-channel DL model, a hybrid DL model, and a clinical model were constructed. The performance of these predictive models was assessed by using receiver operating characteristics (ROC) analysis and decision curve analysis (DCA).

Results
The areas under the curves (AUCs) of the clinical, single-DL, multi-DL, and hybrid-DL models were 0.734 (95% CI, 0.674–0.788), 0.710 (95% CI, 0.649–0.766), 0.767 (95% CI, 0.710–0.819), and 0.857 (95% CI, 0.807–0.898) in the development dataset. The AUC of the hybrid-DL model was significantly higher than the single-DL and multi-DL models (both p < 0.001) in the development dataset, and the single-DL model (p = 0.028) in the testing dataset. Decision curve analysis demonstrated the hybrid-DL model had higher net benefit than other models across the majority range of threshold probabilities.

Conclusions
The proposed hybrid-DL model achieved good predictive efficacy and could be used to predict tumor deposits in rectal cancer.

Critical relevance statement
The proposed hybrid-DL model achieved good predictive efficacy and could be used to predict tumor deposits in rectal cancer.

Key points
• Preoperative non-invasive identification of TDs is of great clinical significance.
• The combined hybrid-DL model achieved good predictive efficacy and could be used to predict tumor deposits in rectal cancer.
• A preoperative nomogram provides gastroenterologist with an accurate and effective tool.

Graphical Abstract
Mesenchymal stem cells and dental implant osseointegration during aging: from mechanisms to therapy
Authors: Ma Yang , Wang Siyuan , Wang Hui , Chen Xiaoyu , Shuai Yi , Wang Huiming , Mao Yingjie , He Fuming 
Published: December 2023

AbstractDental implants are widely used to replace missing teeth, providing patients with unparalleled levels of effectiveness, convenience, and affordability. The biological basis for the clinical success of dental implants is osseointegration. Bone aging is a high-risk factor for the reduced osseointegration and survival rates of dental implants. In aged individuals, mesenchymal stem cells (MSCs) in the bone marrow show imbalanced differentiation with a reduction in osteogenesis and an increase in adipogenesis. This leads to impaired osseointegration and implant failure. This review focuses on the molecular mechanisms underlying the dysfunctional differentiation of aged MSCs, which primarily include autophagy, transcription factors, extracellular vesicle secretion, signaling pathways, epigenetic modifications, microRNAs, and oxidative stress. Furthermore, this review addresses the pathological changes in MSCs that affect osseointegration and discusses potential therapeutic interventions to enhance osseointegration by manipulating the mechanisms underlying MSC aging.
Targeting ST8SIA6-AS1 counteracts KRASG12C inhibitor resistance through abolishing the reciprocal activation of PLK1/c-Myc signaling
Authors: Wang Yafang , Yao Mingyue , Li Cheng , Yang Kexin , Qin Xiaolong , Xu Lansong , Shi Shangxuan , Yu Chengcheng , Meng Xiangjun , Xie Chengying 
Published: December 2023

AbstractBackgroundKRASG12Cinhibitors (KRASG12Ci) AMG510 and MRTX849 have shown promising efficacy in clinical trials and been approved for the treatment of KRASG12C-mutant cancers. However, the emergence of therapy-related drug resistance limits their long-term potential. This study aimed to identify the critical mediators and develop overcoming strategies.MethodsBy using RNA sequencing, RT-qPCR and immunoblotting, we identified and validated the upregulation of c-Myc activity and the amplification of the long noncoding RNA ST8SIA6-AS1 in KRASG12Ci-resistant cells. The regulatory axis ST8SIA6-AS1/Polo-like kinase 1 (PLK1)/c-Myc was investigated by bioinformatics, RNA fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and chromatin immunoprecipitation. Gain/loss-of-function assays, cell viability assay, xenograft models, and IHC staining were conducted to evaluate the anti-cancer effects of co-inhibition of ST8SIA6-AS1/PLK1 pathway and KRAS both in vitro and in vivo.ResultsKRASG12Ci sustainably decreased c-Myc levels in responsive cell lines but not in cell lines with intrinsic or acquired resistance to KRASG12Ci. PLK1 activation contributed to this ERK-independent c-Myc stability, which in turn directly induced PLK1 transcription, forming a positive feedback loop and conferring resistance to KRASG12Ci. ST8SIA6-AS1 was found significantly upregulated in resistant cells and facilitated the proliferation of KRASG12C-mutant cancers. ST8SIA6-AS1 bound to Aurora kinase A (Aurora A)/PLK1 and promoted Aurora A-mediated PLK1 phosphorylation. Concurrent targeting of KRAS and ST8SIA6-AS1/PLK1 signaling suppressed both ERK-dependent and -independent c-Myc expression, synergistically led to cell death and tumor regression and overcame KRASG12Ci resistance.ConclusionsOur study deciphers that the axis of ST8SIA6-AS1/PLK1/c-Myc confers both intrinsic and acquired resistance to KRASG12Ci and represents a promising therapeutic target for combination strategies with KRASG12Ci in the treatment of KRASG12C-mutant cancers.
Discharge mode conversion of bending flexible electrodes
Authors: Zhou Desheng , Li Jiayin , Tang Xin , Kim Minkwan 
Published: December 2023

Abstract
Printed flexible electrodes have attracted widespread attention due to the low-cost process, large-area printing and resource saving. The performances of a flexible electrode in different applications is studied by researchers. In this paper, the characteristics of a flexible electrode with different bending angles are experimentally studied. Electrical, optical and productions characteristics are illustrated to demonstrate the performance of dielectric barrier discharge with a flexible electrode. Furthermore, the electrical fields are studied to explain the transfer of discharge mode and the corresponding discharge products.
The Origin and Distribution of Microzymes (Bacteria) in Water, and the Circumstances which determine their Existence in the Tissues and Liquids of the Living Body
Authors: Burdon-Sanderson John 
Published: December 2023

ABSTRACT
In my previous report on the intimate pathology of contagion, microzymes were defined as living particles which in their earliest state are spheroids, and do not exceed of an inch in diameter, but subsequently elongate into rods. As regards the conditions of their development, their existence was said to be associated with the commencement of putrefactive decomposition of nitrogenous compounds. The question of their origin and destiny was left unanswered. It was left undecided whether on the one hand “they constitute a race of more or less similar individuals, each of which springs from and reproduces its like,” or, on the other, are “germs in which a specific form is wrapped up,” capable of developing to the higher organisms from which they spring.
Note on Immersion Object-Glasses for the Microscope
Authors: Pigott Royston 
Published: December 2023

ABSTRACT
It is a curious fact that, though several writers in this country and America have taken up the question of immersion objectives, very different opinions have been expressed as to the causes of the advantages obtained. One writer boldly asserts that the aperture of an immersion lens can never exceed 80°. The following experiment points to a very different conclusion.
The Luminous Organs and Light of the PennatulÆ
Authors: Panceri  
Published: December 2023

ABSTRACT
The memoir presented to the Academy under the title indicated above commences by the enumeration of the authors who have witnessed the phosphorescence of the zoophites in question. Although omitting the observers who limit themselves to stating the fact that light is emitted by the Pennatulidæ, I ought specially to mention Spallanzani, Blainville, Delle Chiaje, and Forbes, as having already described the luminous waves which are seen traversing these little polypes when they have been recently touched. ‘Hitherto neither methodical experiments have been made towards determining the conditions of this phenomenon, nor special researches to discover whether these animals really possess true luminous organs. Formerly it was generally believed that the mucus which clothed the exterior of the had the power of giving light in such a way that the finger which touched and pressed these little polypes became covered itself with luminous matter.
Microcythœmia; a Morbid Condition of the Blood hitherto undescribed1
Authors: Vanlair  , Masius  
Published: December 2023

ABSTRACT
In this memoir the authors designate by the name of “microcythémie” a disease of which they believe the principal character to consist in a special alteration of the blood morphologically expressed by the presence of an enormous number of red corpuscles different from the ordinary red corpuscles. To these they assign the name “microcytes,” from their small size, and the name microcythœmia is formed on the model of leucocythœmia. The observation of one case furnished the authors with the chief groundwork of their paper, and we shall follow them in prefixing a short relation of it to our summary of the memoir.