bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized comparator-controlled study evaluating efficacy and safety of pembrolizumab plus Bacillus Calmette-Guérin (BCG) in patients with high-risk nonmuscle-invasive bladder cancer (HR NMIBC): KEYNOTE-676 cohort B.
Authors: Kamat Ashish M. , Shariat Shahrokh , Steinberg Gary D. , Alanee Shaheen Riadh , Nishiyama Hiroyuki , Nam Kijoeng , Kapadia Ekta , Shore Neal D. , Hahn Noah M. 
Published: February 2022

TPS597 Background: Cohort A of the phase 2 KEYNOTE-057 study showed that pembrolizumab monotherapy provided effective antitumor activity and acceptable safety in patients with BCG-unresponsive HR NMIBC with carcinoma in situ (CIS). Pembrolizumab in combination with BCG at earlier stages of HR NMIBC might provide benefit superior to that of BCG monotherapy. The open-label, comparator-controlled, phase 3 KEYNOTE-676 study (NCT03711032) will be conducted to investigate the efficacy and safety of pembrolizumab + BCG versus BCG monotherapy in patients with HR NMIBC. Cohort A will enroll patients with persistent or recurrent HR NMIBC after BCG induction. Cohort B is a new, randomly assigned cohort that will help evaluate pembrolizumab + BCG in BCG treatment–naive patients who either never received BCG treatment or received BCG treatment > 2 years before enrollment. Methods: Cohort B of KEYNOTE-676 will enroll approximately 975 patients with blinded independent central review (BICR)–confirmed HR NMIBC (T1, high-grade Ta CIS) and Eastern Cooperative Oncology Group performance status score 0-2 who underwent cystoscopy/transurethral resection of bladder tumor ≤12 weeks before randomization and had not received BCG within the past 2 years. Patients will be randomly assigned 1:1:1 to receive pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) + BCG reduced maintenance (≤6 months), pembrolizumab 400 mg IV Q6W + BCG full maintenance (≤18 months), or BCG monotherapy (BCG full maintenance). Stratification factors include NMIBC stage (CIS or no CIS) and PD-L1 expression (combined positive score [CPS] ≥10 or CPS < 10), determined by central laboratory. Disease status will be assessed by use of cystoscopy, urine cytology, and biopsy (as applicable) every 12 weeks (Q12W) through year 2, then every 24 weeks through year 5; imaging with computed tomography urography will occur every 72 weeks. Adverse events (AEs) will be monitored throughout the study and up to 30 days after cessation of study treatment (90 days for serious AEs). The primary end point is event-free survival (EFS). Secondary end points include complete response rate by BICR, duration of response (DOR), 12-month DOR rate (CIS only), 24-month EFS rate, disease-specific survival, time to cystectomy, overall survival, and safety. The study is enrolling or planning to enroll at sites in Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT03711032.
Biomarker-Based Phase II Study of Sapanisertib (TAK-228): An mTORC1/2 Inhibitor in Patients With Refractory Metastatic Renal Cell Carcinoma
Authors: McGregor Bradley A. , Xie Wanling , Adib Elio , Stadler Walter M. , Zakharia Yousef , Alva Aijai , Michaelson M. Dror , Gupta Shilpa , Lam Elaine T. , Farah Subrina , Nassar Amin H. , Wei Xiao X. , Kilbridge Kerry L. , Harshman Lauren , Signoretti Sabina , Sholl Lynette , Kwiatkowski David J. , McKay Rana R. , Choueiri Toni K. 
Published: February 2022

PURPOSESapanisertib is a kinase inhibitor that inhibits both mammalian target of rapamycin complex 1 (mTORC1) and mTORC2. In this multicenter, single-arm phase II trial, we evaluated the efficacy of sapanisertib in patients with treatment-refractory metastatic renal cell carcinoma (mRCC; NCT03097328 ).METHODSPatients with mRCC of any histology progressing through standard therapy (including prior mTOR inhibitors) had baseline biopsy and received sapanisertib 30 mg by mouth once weekly until unacceptable toxicity or disease progression. The primary end point was objective response rate by RECIST 1.1. Tissue biomarkers of mTOR pathway activation were explored.RESULTSWe enrolled 38 patients with mRCC (clear cell = 28; variant histology = 10) between August 2017 and November 2019. Twenty-four (63%) had received ≥ 3 prior lines of therapy; 17 (45%) had received prior rapalog therapy. The median follow-up was 10.4 (range 1-27.4) months. Objective response rate was two of 38 (5.3%; 90% CI, 1 to 15.6); the median progression-free survival (PFS) was 2.5 months (95% CI, 1.8 to 3.7). Twelve patients (32%) developed treatment-related grade 3 adverse events, with no grade 4 or 5 toxicities. Alterations in the mTOR pathway genes were seen in 5 of 29 evaluable patients ( MTOR n = 1, PTEN n = 3, and TSC1 n = 1) with no association with response or PFS. Diminished or loss of PTEN expression by immunohistochemistry was seen in 8 of 21 patients and trended toward shorter PFS compared with intact PTEN (median 1.9 v 3.7 months; hazard ratio 2.5; 95% CI, 0.9 to 6.7; P = .055).CONCLUSIONSapanisertib had minimal activity in treatment-refractory mRCC independent of mTOR pathway alterations. Additional therapeutic strategies are needed for patients with refractory mRCC.
Pediatric Diabetes on the Rise: Trends in Incident Diabetes During the COVID-19 Pandemic
Authors: Modarelli Rachel , Sarah Salma , Ramaker Megan E , Bolobiongo Mboli , Benjamin Robert , Gumus Balikcioglu Pinar 
Published: February 2022

Abstract

Context
The effects of the coronavirus disease 2019 (COVID-19) pandemic on the incident cases of pediatric type 1 diabetes (T1D) and type 2 diabetes (T2D) are not clear.

Objective
To identify trends in incidence and presentation of pediatric new-onset T1D and T2D during the COVID-19 pandemic.

Methods
A retrospective chart review was conducted. Demographics, anthropometrics, and initial laboratory results from patients ages 0 through 21 years who presented with new-onset diabetes to a pediatric tertiary care center were recorded.

Results
During the pandemic, incident cases of pediatric T1D increased from 31 in each of the prior 2 years to 46; an increase of 48%. Incident cases of pediatric T2D increased by 231% from 2019 to 2020. The number of incident cases of pediatric T2D increased significantly more than the number of incident cases of pediatric T1D (P = 0.009). Patients with T2D were more likely to present in diabetic ketoacidosis (DKA), though this was not statistically significant (P = 0.093). Severe DKA was higher compared with moderate DKA (P = 0.036) in incident cases of pediatric T2D. During the pandemic, for the first time, incident cases of T2D accounted for more than one-half of all newly diagnosed pediatric diabetes cases (53%).

Conclusions
There were more incident pediatric T1D and T2D cases as well as an increase in DKA severity in T2D at presentation during the COVID-19 pandemic. More importantly, incident T2D cases were higher than the incident T1D during the pandemic. This clearly suggests a disruption and change in the pediatric diabetes trends with profound individual and community health consequences.
Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease
Authors: Keshvari Sahar , Genz Berit , Teakle Ngari , Caruso Melanie , Cestari Michelle F. , Patkar Omkar L. , Tse Brian W. C. , Sokolowski Kamil A. , Ebersbach Hilmar , Jascur Julia , MacDonald Kelli P. A. , Miller Gregory , Ramm Grant A. , Pettit Allison R. , Clouston Andrew D. , Powell Elizabeth E. , Hume David A. , Irvine Katharine M. 
Published: February 2022

ABSTRACT
Resident and recruited macrophages control the development and proliferation of the liver. We have previously shown in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte proliferation and promoted repair in models of acute hepatic injury in mice. Here, we investigated the impact of CSF1-Fc on resolution of advanced fibrosis and liver regeneration, using a non-resolving toxin-induced model of chronic liver injury and fibrosis in C57BL/6J mice. Co-administration of CSF1-Fc with exposure to thioacetamide (TAA) exacerbated inflammation consistent with monocyte contributions to initiation of pathology. After removal of TAA, either acute or chronic CSF1-Fc treatment promoted liver growth, prevented progression and promoted resolution of fibrosis. Acute CSF1-Fc treatment was also anti-fibrotic and pro-regenerative in a model of partial hepatectomy in mice with established fibrosis. The beneficial impacts of CSF1-Fc treatment were associated with monocyte-macrophage recruitment and increased expression of remodelling enzymes and growth factors. These studies indicate that CSF1-dependent macrophages contribute to both initiation and resolution of fibrotic injury and that CSF1-Fc has therapeutic potential in human liver disease.
Appearance of an Electrochemical Oxidative Peak of Gold/Bis(trifluoromethylsulfonyl)amide-based Ionic Liquid Interfaces at Elevated Temperatures
Authors: Ueda Hiroyuki , Hisatomi Tomohiro , Yoshimoto Soichiro 
Published: February 2022

Abstract
The electrochemical behavior of a Au(111) electrode was investigated in three ionic liquids (ILs) containing trifluoromethylsulfonyl-based anions at temperatures ranging from 20 °C to 100 °C. Gold oxidation, that is, gold etching, occurred at elevated temperatures (≥70 °C) and was found to be dependent on the chemical structure of the ILs. These results allow us to simplify the procedure of gold dissolution in bis(trifluoromethylsulfonyl)amide-based ILs, thereby improving the efficiency of electrochemical etching.
Heteroatom-incorporated Trimethylenemethane: Synthesis and Properties of Triphenylphenylnitroxide–(Nitronyl Nitroxide) Dyad
Authors: Kumagai Tasuku , Suzuki Shuichi , Kanzaki Yuki , Shiomi Daisuke , Sato Kazunobu , Takui Takeji , Tanaka Rika , Okada Keiji , Kozaki Masatoshi 
Published: February 2022

Abstract
We designed and synthesized a triphenylphenylnitroxide–(nitronyl nitroxide) dyad with a structure isoelectronic with trimethylenemethane. Crystal structure analysis demonstrated that the dihedral angle between the nitroxide and nitronyl nitroxide moieties was excessively small due to the steric effects of the triphenylphenyl moiety. The coplanarity of the two radical systems induced an excessively strong ferromagnetic intramolecular interaction (2J/kB ≥ +2000 K; H = −2JS1/2•S1/2).
Do something or do nothing? anatomical variants and incidental findings on cone beam CT. part 1
Authors: Makdissi Jimmy , Loughlin Amanda , Dungarwalla Mohammed M 
Published: February 2022

Cone beam computed tomography (CBCT) is a popular and often indispensable imaging modality used for the dento-alveolar tissues and immediate surrounding structures. It can be used across several dental disciplines including endodontics, implant planning, oral surgery and orthodontics. Furthermore, it is also commonly used in the medical specialities of oral and maxillofacial surgery (OMFS) and ear, nose and throat (ENT) surgery. In many of the images taken, there will often be findings/presentations that may not be expected, or familiar, to the reporting clinician. CPD/Clinical Relevance: Many incidental findings are innocuous, yet their recognition and documentation are essential because some will warrant medical or surgical intervention.
Total and partial knee arthroplasty implants that maintain native load transfer in the tibia
Authors: Munford Maxwell J. , Stoddart Jennifer C. , Liddle Alexander D. , Cobb Justin P. , Jeffers Jonathan R. T. 
Published: February 2022

Aims Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but the solid metal implants disrupt the natural distribution of stress and strain which can lead to bone loss over time. This generates problems if the implant needs to be revised. This study investigates whether titanium lattice UKA and TKA implants can maintain natural load transfer in the proximal tibia. Methods In a cadaveric model, UKA and TKA procedures were performed on eight fresh-frozen knee specimens, using conventional (solid) and titanium lattice tibial implants. Stress at the bone-implant interfaces were measured and compared to the native knee. Results Titanium lattice implants were able to restore the mechanical environment of the native tibia for both UKA and TKA designs. Maximum stress at the bone-implant interface ranged from 1.2 MPa to 3.3 MPa compared with 1.3 MPa to 2.7 MPa for the native tibia. The conventional solid UKA and TKA implants reduced the maximum stress in the bone by a factor of 10 and caused > 70% of bone surface area to be underloaded compared to the native tibia. Conclusion Titanium lattice implants maintained the natural mechanical loading in the proximal tibia after UKA and TKA, but conventional solid implants did not. This is an exciting first step towards implants that maintain bone health, but such implants also have to meet fatigue and micromotion criteria to be clinically viable. Cite this article: Bone Joint Res 2022;11(2):91–101.
Vitamin D status of patients with systemic inflammatory connective tissue diseases: a cross-sectional study
Authors: Vilms E. A. , Dobrovolskaya E. V. , Turchaninova M. S. , Bykova E. A. , Sohoshko I. A. 
Published: February 2022

Background. In addition to regulating mineral metabolism and bone metabolism, vitamin D is important for supporting structure and other types of connective tissue. Studies have shown the role of vitamin D deficiency in the pathogenesis of systemic inflammatory diseases of the connective tissue, autoimmune diseases. The results of studying this problem in countries with different geographic locations are also of interest.Aim. Comparative assessment of vitamin D status of patients with systemic inflammatory diseases of the connective tissue and patients without rheumatic diseases.Materials and methods. This cross-sectional observational study analyzed the vitamin D supply of the following groups: patients with systemic inflammatory diseases of the connective tissue who do not take vitamin D preparations, patients with systemic inflammatory diseases of the connective tissue who take vitamin D preparations, and «conditionally healthy» individuals, without complaints, examined in the same period comparable in gender and age with the patients of the main group. The vitamin D supply of the studied patients was determined by the level of the content of the vitamin D metabolite calcidiol in the blood serum 25 (OH) D. Study period: January 2019 to December 2020.Results. The data of 625 patients who applied to the Osteoporosis Prevention and Treatment Center for the specified period were analyzed. Among the patients of the main group who did not take vitamin D preparations, a deficiency was revealed in 54.7% of the examined, the optimal provision in 11.2%. The median serum 25 (OH) D concentration was in the range of 19.0 ng / ml deficiency. The study participants belonging to the comparison group had a deficit in 44.1% of cases and an optimal provision in 21.5%. The study group of the main group receiving vitamin D preparations had the maximum number of individuals with the optimal status – 37.0%, while a significant part of the examined had a deficit of varying severity – 29.1%. In addition, this group was characterized by the highest median serum metabolite 25 (OH) D – 26.0 ng / ml.Conclusion. A comparative analysis of the D-vitamin status of patients with systemic inflammatory diseases of the connective tissue and «conditionally healthy» individuals without complaints was carried out, which made it possible to establish differences in the provision depending on the existing disease, as well as depending on the therapy with vitamin D preparations. a lower supply of vitamin D than control group «healthy» individuals. In the case of receiving vitamin subsidies, the provision with it in the group of patients was statistically significantly higher, both in comparison with patients who did not take the vitamin, and in comparison, with individuals from the comparison group.
The Neukirch–Uchida theorem with restricted ramification
Authors: Shimizu Ryoji 
Published: February 2022

Abstract
Let K be a number field and S a set of primes of K.
We write

K
S

/
K

{K_{S}/K}

for the maximal extension of K
unramified outside S and

G

K
,
S

{G_{K,S}}

for its Galois group.
In this paper, we prove the following generalization of the Neukirch–Uchida theorem under some assumptions:
“For

i
=

1
,
2

{i=1,2}

, let

K
i

{K_{i}}

be a number field and

S
i

{S_{i}}

a set of primes of

K
i

{K_{i}}

. If

G

K
1

,

S
1

{G_{K_{1},S_{1}}}

and

G

K
2

,

S
2

{G_{K_{2},S_{2}}}

are isomorphic, then

K
1

{K_{1}}

and

K
2

{K_{2}}

are isomorphic.”
Here the main assumption is that the Dirichlet density of

S
i

{S_{i}}

is not zero for at least one i. A key step of the proof is to recover group-theoretically the l-adic cyclotomic character of an open subgroup of

G

K
,
S

{G_{K,S}}

for some prime number l.
Investigations on the Hardness and Grain Size of Gears made out of Ultra-Clean Gear Steels after Case-Hardening
Authors: Fuchs D. , Fiederling E. , Tobie T. , Stahl K. 
Published: February 2022

KurzfassungHärte und Korngröße von Zahnrädern aus hochreinen Zahnradstählen nach Einsatzhärtung und Kugelstrahlen wurden im Rahmen eines Forschungsprojekts untersucht, dessen Schwerpunkt auf der Bestimmung der Zahnfußtragfähigkeit von einsatzgehärteten, kugelgestrahlten Zahnrädern lag. Die häufigste Versagensart bei diesen hochfesten Zahnrädern ist der Zahnfußbruch, der durch eine Rissinitiierung unterhalb der Oberfläche an einem nicht-metallischen Einschluss verursacht wird (Bruchlinsenversagen, im Englischen: Fisheye failure). Neben solchen Einschlüssen sind auch die Härte und die Abschreckkorngröße dafür bekannt, dass sie einen erheblichen Einfluss auf die Tragfähigkeit eines Zahnrades haben. Um sicherzustellen, dass in diesem Forschungsprojekt ausschließlich der Einfluss von nicht-metallischen Einschlüssen untersucht wird, mussten mögliche Quereinflüsse ausgeschlossen, minimiert oder zumindest bekannt sein. Nach einem ungeeigneten Einsatzhärtungsprozess erreichen Zahnräder jedoch nicht die härtebezogenen Spezifikationen, oder Zahnräder aus Zahnradstählen mit hoher Feinkornstabilität können Mengen an gröberen Körnern enthalten. Daher wurden Einsatzhärtungsparameter abgeleitet und überprüft, ob sie zu den für einsatzgehärtete Zahnradstähle geforderten Korngrößen- und Härtespezifikationen nach ISO 6336 führen. Weiterhin wurde untersucht, wie sich ein reduzierter Aluminiumgehalt bei resultierenden höheren Reinheitsgrad, d. h. kompensiert durch eine Nioblegierung zur Erhaltung der Feinkornstabilität, auf die Korngröße nach dem Einsatzhärten auswirkt.
Gearbox Production Using Distortion Controlled Inductive Fixture Hardening*
Authors: Knauf S. , Buchner K. , Jenne R. 
Published: February 2022

Abstract
Fixture-hardening, also known as quench-press hardening, is a widespread process mainly for the automotive industry. This paper introduces a new inductive hardening and tempering process that combines the well-known advantages of induction heating and hardening with the advantages of a fixture hardening process to obtain highly precise workpieces with enormously reduced or even without rework. The main component is a new hardening machine with implemented fixture hardening assembly and integrated induction coil, all in a protective gas atmosphere. Induction as electrical energy source can be used for heating up workpieces prior to fixture hardening and for tempering, which allows to simultaneously draw out the calibration mandrel without any abrasive wear on its surface. In certain applications, an expanding mandrel can be used in order to relieve the workpiece.
Synthesis of Nanocrystalline B2 Structured (Ru, Ir) Al in the Ternary Ru–Al–Ir System by Mechanical Alloying and its Thermal Stability
Authors: Liu K.W. , Mücklich F. , Pitschke W. , Birringer R. , Wetzig K. 
Published: February 2022

Abstract
B2 structured single-phase (Ru,Ir)Al is synthesized directly in the ternary Ru– Al– Ir system by mechanical alloying. Complete solubility between pseudo-binary RuAl – IrAl is achieved in a composition range 10–25 at.% Ir, while the range for Al remains at 50 at.%. B2 structured (Ru, Ir) Al is formed by an abrupt reaction at the beginning of milling of all three compositions and a certain quantity of Ir was found to remain after the reaction. Further alloying and a reaction between Ir and sticking Al on the surfaces of milling tools take a much longer time and finally result in single phase B2 structured (Ru, Ir) Al. The ternary alloying element Ir has been found to ameliorate the sluggish reactivity of Ru by promoting the abrupt reaction. No decomposition process has been observed for the as-milled single-phase (Ru, Ir) Al by means of high-temperature X-ray diffraction, demonstrating the complete mutual solubility between pseudo-binary RuAl and IrAl in the present composition range. The structural evolution of as-milled materials includes reordering, strain relaxation and grain growth. The grain size of the as-milled (Ru, Ir) Al after exposure to elevated temperatures (up to 1273 K), turns out to be less than 30 nm and reflects its strong thermal stability.
The Al–Ca System, Part 2: Calorimetrie Measurements and Thermodynamic Assessment
Authors: Kevorkov D. , Schmid-Fetzer R. , Pisch A. , Hodaj F. , Colinet C. 
Published: February 2022

Abstract
Drop solution calorimetry was performed to determine the enthalpies of formation of the binary Al2Ca and Al3Ca8 phases and the partial enthalpy of mixing at infinite dilution of calcium in liquid aluminum. A consistent thermodynamic model of the Al–Ca system was constructed for the four stoichiometric compounds Al4Ca, Al2Ca, AlCa and Al3Ca8 and for the liquid phase with a sub-subregular solution model. Optimization of the thermodynamic parameters using the Calphad method was done by incorporating all available experimental data on phase equilibria, enthalpies of formation and mixing and the activity coefficients in the liquid. A consistent description of the phase diagram and thermodynamic properties is presented which is well supported by the experimental data. The Ca-rich part of the phase diagram differs substantially from previous reports, mainly because of the two newly discovered phases AlCa and Al3Ca8.
Interface Motion of β-Silicon Nitride in a Liquid Phase
Authors: Wang Ling-Ling , Tien Tseng-Ying 
Published: February 2022

Abstract
Morphology evolution of β-Si3N4 grains on the end caps has shown significant dynamical features. It has been observed the (0001) growth front experiencing a shape transition on the caps from semisphere to negative-curved configuration. After our previous simplified solution, in this paper, the finite element analysis method has been used to further simulate the tip evolution for the hexagonal β-Si3N4 grains.
Characterization of the metastable austenite in low-alloy FeCMnSi TRIP-aided steel by neutron diffraction
Authors: Barbé L. , Conlon K. , De Cooman B.C. 
Published: February 2022

Abstract
The detailed analysis of X-ray diffraction data obtained from intercritically annealed and isothermally transformed low-alloy FeCMnSi TRIP-aided steels reveals that the microstructure contains athermal plate martensite and Fe2C η carbide in addition to ferrite, bainite and residual austenite. Neutron diffraction shows that athermal plate martensite can be formed at room temperature in the isolated austenite phase. Whereas the formation of athermal martensite leads to compressive strains in the austenite, the formation of strain-induced martensite results in tensile straining of the austenite. The strain-induced transformation leads to the formation of a martensite of low tetragonality. Low-temperature annealing leads to the formation of η carbide in both the athermal and strain-induced martensite.