bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concept and application of the probability of pharmacological success (PoPS) as a decision tool in drug development: a position paper
Authors: Chen Chao , Zhou Xuan , Lavezzi Silvia Maria , Arshad Usman , Sharma Raman 
Published: January 2023

Abstract
Background
In drug development, few molecules from a large pool of early candidates become successful medicines after demonstrating a favourable benefit-risk ratio. Many decisions are made along the way to continue or stop the development of a molecule. The probability of pharmacological success, or PoPS, is a tool for informing early-stage decisions based on benefit and risk data available at the time.

Results
The PoPS is the probability that most patients can achieve adequate pharmacology for the intended indication while minimising the number of subjects exposed to safety risk. This probability is usually a function of dose; hence its computation typically requires exposure–response models for pharmacology and safety. The levels of adequate pharmacology and acceptable risk must be specified. The uncertainties in these levels, in the exposure–response relationships, and in relevant translation all need to be identified. Several examples of different indications are used to illustrate how this approach can facilitate molecule progression decisions for preclinical and early clinical development. The examples show that PoPS assessment is an effective mechanism for integrating multi-source data, identifying knowledge gaps, and forcing transparency of assumptions. With its application, translational modelling becomes more meaningful and dose prediction more rigorous. Its successful implementation calls for early planning, sound understanding of the disease-drug system, and cross-discipline collaboration. Furthermore, the PoPS evolves as relevant knowledge grows.

Conclusion
The PoPS is a powerful evidence-based framework to formally capture multiple uncertainties into a single probability term for assessing benefit-risk ratio. In GSK, it is now expected for governance review at all early-phase decision gates.
Stigma of infidelity associated with condom use explains low rates of condom uptake: qualitative data from Uganda and Tanzania
Authors: Broderick Kathryn , Aristide Christine , Bullington Brooke W. , Mwanga-Amumpaire Juliet , Downs Jennifer A. , Sundararajan Radhika 
Published: January 2023

AbstractDespite widespread messaging supporting male (external) condom use to prevent HIV in endemic settings, utilization of condoms is low across sub-Saharan Africa. A thorough understanding of barriers to condom use as a form of HIV prevention is necessary to reduce HIV transmission. Here, we present qualitative data from rural eastern Africa to explain low utilization of condoms among heterosexual adults. Focus groups and interviews were conducted in Tanzania and Uganda between 2016 and 2019. A content analysis approach was used to identify attitudes about condoms and factors related to use/non-use. We found that strategies such as abstinence and being faithful to one’s partner are perceived as ideal but rarely achievable methods of HIV prevention. Condoms are used in the setting of “failure” to abstain or be faithful and are therefore stigmatized as markers of infidelity. As such, use within cohabiting and long-term relationships is low. Our data suggest that negative perceptions of condoms may stem from persistent effects of the formerly applied “ABC” HIV prevention approach, a public health messaging strategy that described A—abstinence, B—be faithful, and C—use a condom as tiered prevention tools. Condom uptake could increase if HIV prevention messaging acknowledges existing stigma and reframes condom use for proactive health prevention. These studies were approved by Weill Cornell Medicine (Protocols 1803019105 and 1604017171), Mbarara University of Science and Technology (Protocol 16/0117), Uganda National Council of Science and Technology (Protocol SS-4338), and the Tanzania National Institute for Medical Research (Protocol NIMR/HQ/R.8c/Vol.I/1330).
Development of SARS-CoV-2 specific IgG and IgA antibodies in serum and milk with different SARS-COV-2 vaccines in lactating women
Authors: Lechosa-Muñiz Carolina , Paz-Zulueta María , Irure-Ventura Juan , Mendez-Legaza Jose Manuel , Cuesta González Rocío , Gómez-Acebo Inés , López-Hoyos Marcos , Llorca Javier , Cabero-Pérez María Jesús 
Published: January 2023

Abstract
Background
Our main objective was to determine the evolution of IgG and IgA antibodies directed against SARS-CoV-2 protein S in the blood of lactating women and in breast milk.

Methods
A cohort of 110 uninfected and vaccinated breastfeeding women was followed-up for 6 months at the Marqués de Valdecilla University Hospital, Spain, in 2020. An additional group of 23 breastfeeding mothers who had no previously documented infection and had not been vaccinated against SARS-CoV-2 were included as a control group. The antibodies in blood and breast milk and their evolution at 6 months post-vaccination were analysed.

Results
One hundred ten breastfeeding mothers were included; 70 women (63.6%) were vaccinated with two doses of BNT162b2, 20 women (18.2%) received two doses of mRNA-1273, and 20 women (18.2%) received a single dose of ChAdOx1-S. No evidence of differences between concentrations of antibodies was found according to the type of vaccine, with the exception of serum IgA antibodies, which was higher in women vaccinated with mRNA-1273: mean [95%CI]: 0.05 AU/mL [0.03,0.06] with mRNA-1273, 0.02 AU/mL [0.01,0.03] with BNT162b2 and 0.01 AU/mL [0.00,0.03] with ChAdOx1-S, ANOVA p value = 0.03. The lack of difference between vaccines was also found when anti-S1 specific IgG in serum and breast milk were measured.

Conclusions
In lactating women vaccinated against COVID-19, anti-SARS-CoV-2 antibodies can be detected in both serum and breastmilk 6 months after receiving the second dose, although their concentrations decreased when compared with concentrations reached immediately after vaccination.
Silica coated high performance oxide ceramics promote greater ossification than titanium implants: an in vivo study
Authors: Migliorini Filippo , Schenker Hanno , Betsch Marcel , Maffulli Nicola , Tingart Markus , Hildebrand Frank , Lecouturier Sophie , Rath Björn , Eschweiler Jörg 
Published: January 2023

Abstract
Background
This in vitro study investigated the osseointegration and implant integration of high performance oxide ceramics (HPOC) compared to titanium implants in rabbits.

Methods
Histomorphometry was conducted around the distal, proximal, medial, and lateral aspects of the HPOC to quantify the amount of mature and immature ossification within the bone interface. Histomorphometry was conducted by a trained musculoskeletal pathologist. The region of interest (ROI) represented the percentage of surrounding area of the implant. The percentage of ROI covered by osteoid implant contact (OIC) and mature bone implant contact (BIC) were assessed. The surrounding presence of bone resorption, necrosis, and/or inflammation were quantitatively investigated.

Results
All 34 rabbits survived the 6- and 12-week experimental period. All HPOC implants remained in situ. The mean weight difference from baseline was + 647.7 mg (P < 0.0001). The overall OIC of the ceramic group was greater at 6 weeks compared to the titanium implants (P = 0.003). The other endpoints of interest were similar between the two implants at all follow-up points. No difference was found in BIC at 6- and 12-weeks follow-up. No bone necrosis, resorption, or inflammation were observed.

Conclusion
HPOC implants demonstrated a greater osteoid implant contact at 6 weeks compared to the titanium implants, with no difference found at 12 weeks. The percentage of bone implant contact of HPOC implants was similar to that promoted by titanium implants.
Prevalence of chronic low back pain and its associated factors in the general population of South Korea: a cross-sectional study using the National Health and Nutrition Examination Surveys
Authors: Park Hyun-Jin , Choi Jun-Young , Lee Woo Myung , Park Sang-Min 
Published: January 2023

Abstract
Background
Many factors associated with chronic low back pain (CLBP) have been proposed, including individual, psychosocial, and physical factors. However, these associated factors are still controversial.

Purpose
(1) To determine the prevalence of CLBP and (2) to analyze factors associated with CLBP in the general population using a nationally representative sample of South Koreans.

Study design
Cross-sectional study.

Patient sample
Data from versions IV-1, -2, and -3 of the Korea National Health and Nutrition Examination Survey (KNHANES), which were performed in 2007, 2008, and 2009, respectively (n = 24,871).

Outcome measures
Multiple logistic regression analysis was performed to determine the association between several factors (age, gender, alcohol consumption, household income, education level, mid-intensity physical activity, depressive symptoms, vitamin D level, and comorbidities [stroke, ischemic heart disease, knee osteoarthritis, asthma, COPD, cancer history]) and CLBP.

Methods
CLBP status was surveyed using a self-reported questionnaire. Demographic, socioeconomic status, comorbidities, and other factors were evaluated from health questionnaires, health and physical examinations, and laboratory tests. To analyze the association between these factors and CLBP, we used multiple logistic regression analysis.

Results
Data from 17,038 participants were included in the final analysis, including 2,693 with CLBP and 14,345 without. The prevalence of CLBP was 15.8% in South Korean subjects, with a prevalence of 11.8% in men and 24.5% in women. After regression analysis, we found advanced age, female gender, mid-intensity physical activity, depressive symptoms, stroke, ischemic heart disease, knee arthritis, asthma, COPD, and cancer history were positively associated with CLBP. In contrast, alcohol consumption ≥ 1 drink per month, increased household income, higher education level, and vitamin D insufficiency were negatively associated with CLBP.

Conclusions
Our study showed that CLBP was most common in the elderly and women in the general South Korean population. Several individual, socioeconomic, lifestyle, and health-related factors were associated with CLBP. These results demonstrate the influence of these factors on CLBP in the general population and suggest that consideration of these factors may improve the management of CLBP.
Proteomics investigation of human sera for determination of postoperative indicators of pulmonary cystic echinococcosis
Authors: Sadjjadi Fatemeh Sadat , Hajjaran Homa , Sedaghat Bahareh , Mardani Parviz , Sadjjadi Seyed Mahmoud 
Published: January 2023

Abstract
Background
Cystic echinococcosis (CE)/hydatidosis is an important zoonotic parasitic disease caused by the larval stage of Echinococcus granulosus. The disease is a major health problem all over the world. Finding specific and sensitive biomarkers for follow-up of CE in patients after surgery is essential. Using proteomics methods, the present study aimed to evaluate post-surgical treatment by finding probable biomarker/s in the serum of human lungs CE.

Methods
A total of 24 human sera were tested. These sera included eight confirmed lung/s CE patients sera before surgery (BS), eight sera 12 months post-surgery (12MPS) as well as eight control sera from healthy people. Proteomics methods including 2DE and LC–MS/MS were performed on the specimens followed by bioinformatics analysis. Differentially expressed proteins (DEP) were detected and, separately integrated with protein–protein interaction (PPI) data to construct the PPI network.

Results
A total of 171 protein spots were detected in three groups including BS, 12MPS, and control groups; of which a total of 106 DEP have been expressed based on fold changes > = 2 and p-value < 0.05. More analysis was performed and a total of 10 protein spots were selected for identification by mass spectrometry showing the following proteins: APOA1, BGN, SPP2, EAF1, ACOXL, MRPL55, MCTP2, SEPTIN1, B4GALNT1, and ZNF843. Based on centrality parameters of the PPI network (degree and betweenness) five Hub-bottlenecks proteins with significant centrality values were found including APOA1, BGN, SPP2, EAF1, and ACOXL.

Conclusion
This study showed five proteins as hub-bottleneck proteins; of which APOA1 was more prominent. It can be concluded that a change in expression of this protein in patients’ sera could be used as an indicator tool for the achievement of lungs CE surgical therapy.
Psychiatric disorders, personality and neuropsychological alterations in Erdheim-Chester disease
Authors: Soumet-Leman Charlotte , Rotge Jean-Yves , Delavaud Pauline , Amoura Zahir , Cohen-Aubart Fleur , Haroche Julien 
Published: January 2023

AbstractAlthough neurological manifestations and changes in brain volumes have been described in Erdheim-Chester disease (ECD), it remains unknown whether ECD may be associated with psychiatric symptoms and cognitive dysfunctions. We assessed the presence of psychiatric disorders, changes in temperaments and characters, and neuropsychological performances in 32 ECD patients (mean age = 59) younger than 70, not treated with interferon alpha during the last 6 months, and without other serious illnesses. ECD patients exhibited high level of past depressive disorder (80%) and anxiety disorder, especially agoraphobia (29%). They revealed personality changes, especially with high agreeableness (t = 3.18, p < 0.005) and high conscientiousness (t = 3.81, p < 0.001). Neuropsychological assessments showed impairments in attention (GZ: t = 16.12, p < 0.0001, KL: t = 37.01, p < 0.0001) and episodic memory performances (STIR: t = − 3.01, p = 0.006, LTFR: t = − 2.87, p = 0.008, LTIR: t = − 3.63, p = 0.001). Executive functions, such as flexibility, inhibitory control, were unimpaired. Although it remains to be clarified whether these psychiatric symptoms and cognitive impairments may impact the daily functioning and the quality of life, the present study highlights the need to consider cognitive and emotional states in ECD management.
Tumor biomarkers and efficacy in patients treated with trastuzumab emtansine + pertuzumab versus standard of care in HER2-positive early breast cancer: an open-label, phase III study (KRISTINE)
Authors: de Haas Sanne L. , Slamon Dennis J. , Martin Miguel , Press Michael F. , Lewis Gail D. , Lambertini Chiara , Prat Aleix , Lopez-Valverde Vanesa , Boulet Thomas , Hurvitz Sara A. 
Published: January 2023

Abstract
Background
KRISTINE is an open-label, phase III study of trastuzumab emtansine + pertuzumab (T-DM1 + P) versus docetaxel + carboplatin + trastuzumab + pertuzumab (TCH + P) in patients with HER2-positive, stage II–III breast cancer. We investigated the association of biomarkers with clinical outcomes in KRISTINE.

Methods
Patients were randomized to receive neoadjuvant T-DM1 + P or TCH + P and assessed for pathologic complete response (pCR; ypT0/is, ypN0). HER2 status (per central assessment), hormone receptor status, PIK3CA mutation status, HER2/HER3 mRNA levels, tumor-infiltrating lymphocyte levels, PD-L1 status, and NanoString data were analyzed. pCR rates by treatment arm were compared across biomarker subgroups. Analyses were descriptive.

Results
Biomarker analyses included data from all 444 patients (T-DM1 + P, n = 223; TCH + P, n = 221) enrolled in KRISTINE. Biomarker distribution was balanced across treatment arms. All subgroups with higher HER2 amplification/expression and immune marker levels showed numerically higher pCR rates in both arms. Mutated versus non-mutated PIK3CA tumors were associated with numerically lower pCR rates in the T-DM1 + P arm but not in the TCH + P arm. In a multivariate analysis, Prediction Analysis of Microarray with the 50-gene classifier (PAM50) HER2-enriched subtype, HER2 gene ratio ≥ 4, and PD-L1-positive status positively influenced the pCR rate. Biomarkers associated with lower pCR rates (e.g., low HER2 levels, positive hormone receptor status, mutated PIK3CA) were more likely to co-occur. Dynamic on-treatment biomarker changes were observed. Differences in the treatment effects for T-DM1 + P versus TCH + P were similar to those observed in the intent-to-treat population for the majority of the biomarker subgroups.

Conclusions
Although our biomarker analysis did not identify a subgroup of patients that benefited from neoadjuvant T-DM1 + P versus TCH + P, the data revealed that patients with higher HER2 amplification/expression and immune marker levels had improved response irrespective of treatment arm. These analyses confirm the role of HER2 tumor biology and the immune microenvironment in influencing pCR in the neoadjuvant setting and reaffirm the molecular diversity of HER2-positive breast cancer.
Trial Registration: ClinicalTrials.gov NCT02131064. Registered 06 May 2014.
Lrig1 expression identifies quiescent stem cells in the ventricular-subventricular zone from postnatal development to adulthood and limits their persistent hyperproliferation
Authors: Nam Hyung-song , Capecchi Mario R. 
Published: January 2023

Abstract
Background
We previously identified Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1) as a marker of long-term neurogenic stem cells in the lateral wall of the adult mouse brain. The morphology of the stem cells thus identified differed from the canonical B1 type stem cells, raising a question about their cellular origin. Thus, we investigated the development of these stem cells in the postnatal and juvenile brain. Furthermore, because Lrig1 is a known regulator of quiescence, we also investigated the effect(s) of its deletion on the cellular proliferation in the lateral wall.

Methods
To observe the development of the Lrig1-lineage stem cells, genetic inducible fate mapping studies in combination with thymidine analog administration were conducted using a previously published Lrig1T2A-iCreERT2 mouse line. To identify the long-term consequence(s) of Lrig1 germline deletion, old Lrig1 knock-out mice were generated using two different Lrig1 null alleles in the C57BL/6J background. The lateral walls from these mice were analyzed using an optimized whole mount immunofluorescence protocol and confocal microscopy.

Results
We observed the Lrig1-lineage labeled cells with morphologies consistent with neurogenic stem cell identity in postnatal, juvenile, and adult mouse brains. Interestingly, when induced at postnatal or juvenile ages, morphologically distinct cells were revealed, including cells with the canonical B1 type stem cell morphology. Almost all of the presumptive stem cells labeled were non-proliferative at these ages. In the old Lrig1 germline knock-out mice, increased proliferation was observed compared to wildtype littermates without concomitant increase in apoptosis.

Conclusions
Once set aside during embryogenesis, the Lrig1-lineage stem cells remain largely quiescent during postnatal and juvenile development until activation in adult age. The absence of premature proliferative exhaustion in the Lrig1 knock-out stem cell niche during aging is likely due to a complex cascade of effects on the adult stem cell pool. Thus, we suggest that the adult stem cell pool size may be genetically constrained via Lrig1.
Cross-cultural adaptation, validity, reliability and responsiveness of the Japanese version of the Victorian Institute of sports assessment for patellar tendinopathy (VISA-P-J)
Authors: Togashi Ishin , Nagao Masashi , Nishio Hirofumi , Nozu Shojiro , Shiota Yuki , Takazawa Yuji 
Published: January 2023

Abstract
Background
This study aimed to translate, adapt, and test the psychometric properties of the Japanese version of the Victorian Institute of sports assessment for patellar tendinopathy (VISA-P-J).

Methods
This prospective cohort study registered 43 participants ≥ 18 years old with a history of painful symptoms in the inferior pole of the patella to the proximal patellar tendon lasting ≥ 1 month for patellar tendinopathy. Pain in daily life and during sports activities, symptom classification, and patient global impression of change were assessed at the baseline, 1 week, and 12 weeks. The psychometric properties, test–retest reliability, standard error of measurement, internal consistency criterion validity, construct validity, responsiveness, and interpretability, of the VISA-P-J were calculated according to the COSMIN.

Results
The two-way random-effects, absolute agreement intraclass correlation coefficient for test–retest reliability of VISA-P-J was 0.87 (95% confidence interval: 0.78, 0.93), and the standard error of measurement of VISA-P-J was 0.89. The Cronbach's alpha for internal consistency of VISA-P-J was 0.81. A correlation between VISA-P-J and Roel’s classification, Visual Analog Scale for pain (VAS)-Active Daily Living, and VAS-Sports (r = − 0.52, r = − 0.66, r = − 0.86, p < 0.01, respectively) was observed for criterion validity. All hypotheses of the hypothesis-testing method to evaluate construct validity and responsiveness of VISA-P-J were substantiated. The minimal clinically important difference of VISA-P-J was 7 points.

Conclusion
We demonstrated that the VISA-P-J was a reliable, valid, and responsive assessment method for individuals with chronic pain in the patellar tendon.
New Minkowski and related inequalities via general kernels and measures
Authors: Iqbal Sajid , Samraiz Muhammad , Khan Muhammad Adil , Rahman Gauhar , Nonlaopon Kamsing 
Published: January 2023

AbstractIn this article, we introduce a class of functions $\mathfrak{U}(\mathfrak{p})$
U
(
p
)
with integral representation defined over a measure space with σ-finite measure. The main purpose of this paper is to extend the Minkowski and related inequalities by considering general kernels. As a consequence of our general results, we connect our results with various variants for the fractional integrals operators. Such applications have wide use and importance in the field of applied sciences.
Comparison of the accuracy of three intraocular lens power calculation formulas in cataract patients with prior radial keratotomy
Authors: Li Meng , Wang Jin-Da , Zhang Jing-Shang , Mao Ying-Yan , Cao Kai , Wan Xiu-Hua 
Published: January 2023

Abstract
Purpose
To compare the accuracy of three intraocular lens (IOL) formulas in Chinese cataract patients with prior radial keratotomy (RK).

Methods
Medical records of cataract patients with prior RK at Beijing Tongren Hospital were retrospectively analysed. The absolute error (AE) was calculated as the absolute difference between the actual postoperative spherical equivalent and the predicted spherical equivalent. The AE and percentages of eyes with AE within 0.5D, 1.0D, and 2.0D for three formulas [Barrett True-K, Holladay 1 (D–K), Haigis] were calculated and compared.

Results
Forty-seven eyes of 28 cataract patients were included. The Median AE (MedAE) was significantly different among the three formulas (P < 0.001). The MedAE was lowest for the Barrett True-K formula (0.62), followed by the Haigis (0.76), and Holladay 1 (D–K) (1.16). The percentages of eyes with AE within 0.5D, and 1.0D were significantly different among the 3 formulas (P = 0.009, and P < 0.001). The Barrett True-K formula achieved the highest percentages (46.8%) of eyes with AE within 0.5D. Haigis achieved the highest percentages (70.21%) of eyes with AE within 1.0 D.

Conclusions
Barrett True-K is the most accurate IOL power calculation formula among the 3 formulas and Haigis is an alternative choice. Considering the relatively lower accuracy of IOL formulas in cataract patients with prior RK, newer and more accurate IOL formulas are desirable.