bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 3, randomized, double-blind, active-controlled clinical trial to compare BAT1806/BIIB800, a tocilizumab biosimilar, with tocilizumab reference product in participants with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate: treatment period 2 analysis (week 24 to week 48)
Authors: Leng Xiaomei , Leszczyński Piotr , Jeka Slawomir , Liu Shengyun , Liu Huaxiang , Miakisz Malgorzata , Gu Jieruo , Kilasonia Lali , Stanislavchuk Mykola , Yang Xiaolei , Zhou Yinbo , Dong Qingfeng , Mitroiu Marian , Addison Janet , Rezk Mourad F. , Zeng Xiaofeng 
Published: September 2024

Abstract
Background
Equivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24–48).

Methods
In this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated.

Results
Of 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported.

Conclusion
In TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups.

Trial registration
NCT03830203 and EudraCT 2018-002202-31.
Histological observations and transcriptome analyses reveal the dynamic changes in the gonads of the blotched snakehead (Channa maculata) during sex differentiation and gametogenesis
Authors: Zhang Xiaotian , Wu Yuxia , Zhang Yang , Zhang Jin , Chu Pengfei , Chen Kunci , Liu Haiyang , Luo Qing , Fei Shuzhan , Zhao Jian , Ou Mi 
Published: September 2024

Abstract
Background
Blotched snakehead (Channa maculata) displays significant sexual dimorphism, with males exhibiting faster growth rates and larger body sizes compared to females. The cultivation of the all-male population of snakeheads holds substantial economic and ecological value. Nonetheless, the intricate processes governing the development of bipotential gonads into either testis or ovary in C. maculata remain inadequately elucidated. Therefore, it is necessary to determine the critical time window of sex differentiation in C. maculata, providing a theoretical basis for sex control in production practices.

Methods
The body length and weight of male and female C. maculata were measured at different developmental stages to reveal when sexual dimorphism in growth initially appears. Histological observations and spatiotemporal comparative transcriptome analyses were performed on ovaries and testes across various developmental stages to determine the crucial time windows for sex differentiation in each sex and the sex-related genes. Additionally, qPCR and MG2C were utilized to validate and locate sex-related genes, and levels of E2 and T were quantified to understand sex steroid synthesis.

Results
Sexual dimorphism in growth became evident starting from 90 dpf. Histological observations revealed that morphological sex differentiation in females and males occurred between 20 and 25 dpf or earlier and 30–35 dpf or earlier, respectively, corresponding to the appearance of the ovarian cavity or efferent duct anlage. Transcriptome analyses revealed divergent gene expression patterns in testes and ovaries after 30 dpf. The periods of 40–60 dpf and 60–90 dpf marked the initiation of molecular sex differentiation in females and males, respectively. Male-biased genes (Sox11a, Dmrt1, Amh, Amhr2, Gsdf, Ar, Cyp17a2) likely play crucial roles in male sex differentiation and spermatogenesis, while female-biased genes (Foxl2, Cyp19a1a, Bmp15, Figla, Er) could be pivotal in ovarian differentiation and development. Numerous biological pathways linked to sex differentiation and gametogenesis were also identified. Additionally, E2 and T exhibited sexual dimorphism during sex differentiation and gonadal development. Based on these results, it is hypothesized that in C. maculata, the potential male sex differentiation pathway, Sox11a–Dmrt1–Sox9b, activates downstream sex-related genes (Amh, Amhr2, Gsdf, Ar, Cyp17a2) for testicular development, while the antagonistic pathway, Foxl2/Cyp19a1a, activates downstream sex-related genes (Bmp15, Figla, Er) for ovarian development.

Conclusions
This study provides a comprehensive overview of gonadal dynamic changes during sex differentiation and gametogenesis in C. maculata, establishing a scientific foundation for sex control in this species.
Lactated Ringers, albumin and mannitol as priming during cardiopulmonary bypass reduces pulmonary edema in rats compared with hydroxyethyl starch
Authors: Beukers Anne M. , van Leeuwen Anoek L. I. , Ibelings Roselique , Tuip-de Boer Anita M. , Bulte Carolien S. E. , Eberl Susanne , van den Brom Charissa E. 
Published: September 2024

Abstract
Background
Endothelial disorders with edema formation and microcirculatory perfusion disturbances are common in cardiac surgery with cardiopulmonary bypass (CPB) and contribute to disturbed tissue oxygenation resulting in organ dysfunction. Albumin is protective for the endothelium and could be a useful additive to CPB circuit priming. Therefore, this study aimed to compare organ edema and microcirculatory perfusion in rats on CPB primed with lactated Ringers, albumin and mannitol (LR/albumin/mannitol) compared to 6% hydroxyethyl starch (HES).

Results
Male rats were subjected to 75 min of CPB primed with either LR/albumin/mannitol or with 6% HES. Renal and lung edema were determined by wet/dry weight ratio. Pulmonary wet/dry weight ratio was lower in rats on CPB primed with LR/albumin/mannitol compared to HES (4.77 [4.44–5.25] vs. 5.33 [5.06–6.33], p = 0.032), whereas renal wet/dry weight ratio did not differ between groups (4.57 [4.41–4.75] vs. 4.51 [4.47–4.73], p = 0.813). Cremaster microcirculatory perfusion was assessed before, during and after CPB with intravital microscopy. CPB immediately impaired microcirculatory perfusion compared to baseline (LR/albumin/mannitol: 2 [1–7] vs. 14 [12–16] vessels per recording, p = 0.008; HES: 4 [2–6] vs. 12 [10–13] vessels per recording, p = 0.037), which persisted after weaning from CPB without differences between groups (LR/albumin/mannitol: 5 [1–9] vs. HES: 1 [0–4], p = 0.926). In addition, rats on CPB primed with LR/albumin/mannitol required less fluids to reach sufficient flow rates (0.5 [0.0–5.0] mL vs. 9 [4.5–10.0], p < 0.001) and phenylephrine (20 [0–40] µg vs. 90 [40–200], p = 0.004). Circulating markers for inflammation (interleukin 6 and 10), adhesion (ICAM-1), glycocalyx shedding (syndecan-1) and renal injury (NGAL) were determined by ELISA or Luminex. Circulating interleukin-6 (16 [13–25] vs. 33 [24–51] ng/mL, p = 0.006), interleukin-10 (434 [295–782] vs. 2120 [1309–3408] pg/ml, p < 0.0001), syndecan-1 (5 [3–7] vs. 15 [11–16] ng/mL, p < 0.001) and NGAL (555 [375–1078] vs. 2200 [835–3671] ng/mL, p = 0.008) were lower in rats on CPB primed with LR/albumin/mannitol compared to HES.

Conclusion
CPB priming with LR, albumin and mannitol resulted in less pulmonary edema, renal injury, inflammation and glycocalyx degradation compared to 6% HES. Furthermore, it enhanced hemodynamic stability compared with HES. Further research is needed to explore the specific role of albumin as a beneficial additive in CPB priming.
Genome-wide identification of cannabinoid biosynthesis genes in non-drug type Cannabis (Cannabis sativa L.) cultivar
Authors: Sng Benny Jian Rong , Jeong Yu Jeong , Leong Sing Hui , Jeong Jae Cheol , Lee Jiyoung , Rajani Sarojam , Kim Cha Young , Jang In-Cheol 
Published: September 2024

Abstract
Background
Cannabis sativa cultivars can be classified as marijuana or hemp, depending on its amount of the psychoactive cannabinoid Δ9‐tetrahydrocannabinolic acid (THCA). Hemp Cheungsam is a non-drug type Cannabis sativa that is characterized by low THCA content. However, the transcripts and expression profile of cannabinoid biosynthesis pathway genes of hemp Cheungsam have not been investigated.

Methods
RNA-sequencing (RNA-seq) was performed on three different tissue types (flower, leaf, and stem) of hemp Cheungsam to understand their transcriptomes. The expression of cannabinoid biosynthesis pathway genes was further analyzed in each tissue type. Multiple sequence alignment and conserved domain analyses were used to investigate the homologs of cannbinoid biosynthesis genes.

Results
We found that the cannabinoid biosynthesis pathway was mainly expressed in the flowers of hemp Cheungsam, similar to other Cannabis cultivars. However, expression of cannabidiolic acid (CBDA) synthase was much higher than THCA synthase and cannabichromenic acid (CBCA) synthase, suggesting that the transcription profile favors CBDA biosynthesis. Sequence analysis of cannabinoid biosynthesis pathway genes suggested the identity of orthologs in hemp Cheungsam.

Conclusions
Cannabinoid biosynthesis in hemp Cheungsam mostly occurs in the flowers, compared to other plant organs. While CBDA synthase expression is high, THCA and CBCA synthase expression is considerably low, indicating lesser THCA biosynthesis and thus low THCA content. Sequence analysis of key genes (CBDA, THCA, and CBCA synthases) of the cannabinoid biosynthetic pathway indicates that orthologs are present in hemp Cheungsam.
Proposed Denosumab Biosimilar SB16 vs Reference Denosumab in Postmenopausal Osteoporosis: Phase 3 Results Up to Month 12
Authors: Langdahl Bente , Chung Yoon-Sok , Plebanski Rafal , Czerwinski Edward , Dokoupilova Eva , Supronik Jerzy , Rosa Jan , Mydlak Andrzej , Rowińska-Osuch Anna , Baek Ki-Hyun , Urboniene Audrone , Mordaka Robert , Ahn Sohui , Rho Young Hee , Ban Jisuk , Eastell Richard 
Published: September 2024

Abstract

Context
SB16 is a proposed biosimilar to reference denosumab (DEN; brand name: Prolia).

Objective
This phase 3 randomized, double-blind, multicenter study evaluated the biosimilarity of SB16 to DEN in women with postmenopausal osteoporosis (NCT04664959).

Design
The study included 457 postmenopausal osteoporosis patients who had a lumbar spine or total hip T-score between −2.5 and −4. Patients were randomized in a 1:1 ratio to receive either 60 mg of SB16 or DEN subcutaneously at month 0 and month 6. At month 12, patients were rerandomized to continue with the assigned treatment or switch from DEN to SB16 up to month 18. This report includes results up to month 12.

Methods
The primary endpoint was the percent change from baseline in lumbar spine bone mineral density (BMD) at month 12. Secondary endpoints including the percent change from baseline in BMD of the lumbar spine (except for month 12), total hip, and femoral neck; pharmacokinetic, pharmacodynamic (serum C-telopeptide of type I collagen, and procollagen type I N-terminal propeptide), safety, and immunogenicity profiles were measured up to month 12.

Results
The least-squares mean differences in percent change from baseline in lumbar spine BMD at month 12 were 0.33% (90% CI, −0.25 to 0.91) in the full analysis set and 0.39% (95% CI, −0.36 to 1.13) in the per-protocol set; both within the predefined equivalence margin. The secondary endpoints were comparable between the 2 treatment groups.

Conclusion
The reported efficacy, pharmacokinetic, pharmacodynamic, safety, and immunogenicity data support the biosimilarity of SB16 to DEN.
Hematologic Malignancies: Two Cases of a Rare Cause of Hypopituitarism
Authors: Lauzon Brian , Abu-Hijleh Tala , McInnes Natalia , Prebtani Ally 
Published: September 2024

Abstract
Hematologic malignancies are rare causes of sellar masses and hypopituitarism. We report 2 cases of hypopituitarism due to sellar masses from hematologic malignancies. The first patient was found to have hypopituitarism but initial non-gadolinium-enhanced magnetic resonance imaging (MRI) sella did not demonstrate a mass. Subsequent gadolinium-enhanced MRI and transsphenoidal biopsy confirmed a diagnosis of intravascular lymphoma. Treatment with systemic chemotherapy resulted in resolution of abnormalities on MRI. The second patient had a known diagnosis of chronic lymphocytic leukemia, and sellar involvement contributing to hypopituitarism was confirmed on biopsy. Treatment with ibrutinib, acalabrutinib, and stereotactic radiosurgery resulted in resolution of abnormalities on MRI. Both patients were treated with hormone replacement for hypopituitarism. These cases highlight that hematologic malignancies should be suspected as causes of sellar masses/hypopituitarism in patients with concurrent symptoms atypical for a pituitary adenoma (eg, constitutional symptoms), known diagnoses of hematologic malignancies, or rapid tumor growth and invasion on imaging. Gadolinium-enhanced MRI should be pursued if nonenhanced MRI is nondiagnostic. Transsphenoidal biopsy can be considered for diagnosis. Malignancy-directed systemic therapy may improve hypopituitarism and radiographic abnormalities on MRI.
Perilaku Ekonomi dan Dampak Risikonya Bank Syariah di Yogyakarta dalam Pembiayaan <i>Mudarabah</i> dan <i>Murabahah </i>bagi Dana Deposan
Authors: Mughits Abdul 
Published: September 2024

This research tries to check the potency of risk of Islamic bank in defrayal of muḍārabah and murābaḥah. This research was inspired from ascription of whereas one who said that the Islamic banks have not been risk because they have owned the guidance of risk management published by Bank Indonesia (BI). One way to assess the existence of potency of risk of Islamic bank in its defrayal product is using the theory of behavioral economics which’s in general differentiated to two categories, that is rational that which tends to be risk and irrasional that which tend to be not risk. Rational behavior is presented by the approach of efficiency market hyphotesis (EMH) and irrational behavior is presented by the approach of adaptive market hypothesis (AMH) And behavioral finance (BF). This research objects are four Islamic banks in Yogyakarta. After conducting by tracing of field data then found that four Islamic banks affirm still face the risk in their operational, especially operational risk, risk of credit and risk of liquidity. Four banks show that their behaviors are irrasional because tend to show the behavior of AMH and BF, than EMH. Thereby its risk potency tends to minimizes to rate of return of clients of deposan or third party lenders (DPK).

Penelitian ini mencoba untuk melihat potensi risiko bank syariah dalam pembiayaan muḍārabah dan murābaḥah. Penelitian ini terinspirasi dari anggapan yang mengatakan bahwa bank syariah tidak memiliki risiko karena telah memiliki pedoman manajemen risiko yang diterbitkan oleh Bank Indonesia (BI). Salah satu cara untuk melihat adanya potensi risiko bank syariah dalam produk pembiayaan adalah dengan menggunakan teori ekonomi perilaku yang secara umum dibedakan menjadi dua kategori, yaitu perilaku rasional yang cenderung berisiko dan perilaku irasional yang cenderung tidak berisiko. Perilaku rasional dipresentasikan dengan pendekatan efficiency market hyphotesis (EMH) dan perilaku irasional dipresentasikan dengan pendekatan adaptive market hyphotesis (AMH) dan behavioral finance (BF). Objek penelitian ini adalah empat bank syariah di Yogyakarta. Setelah melakukan penelusuran data lapangan maka ditemukan bahwa keempat bank syariah tersebut menegaskan masih menghadapi risiko dalam operasionalnya, terutama risiko operasional, risiko kredit dan risiko likuiditas. Keempat bank tersebut menunjukkan bahwa perilakunya tidak rasional karena cenderung menunjukkan perilaku AMH dan BF dibandingkan EMH. Dengan demikian potensi risikonya cenderung meminimalkan tingkat pengembalian nasabah deposan atau dana pihak ketiga (DPK).
Cypriot Fabrics? White Slip Pottery and Élite Linen Clothes of the Late Bronze Age
Authors: Yasur-Landau Assaf , Spinazzi-Lucchesi Chiara 
Published: September 2024

Abstract
In this article we will point to the similarity between the decoration on Cypriot White Slip (WS) I and II pottery and contemporary 15th–14th-century BCE “Syrian” elite garments shown in 18th Dynasty Egyptian tombs. Depiction of men and women in the tombs of Rekhmire (TT100), Sobekhotep (TT63), Menkheperraseneb (TT86), and Anen (TT120) show white clothes decorated with both vertical and horizontal elements, with dotted and wavy additions. Such elements find direct parallels in the WS I decorative “vocabulary.” We will examine the possibility that the Cypriot WS pottery imitates elite linen clothing produced during the international Late Bronze Age, some even on Cyprus, as indicated by the mention of “linen of Alashiya” (gad

uru

Alašiya) in Hittite inventory texts.
Asymmetric bi-level dual-core mode converter for high-efficiency and polarization-insensitive O-band fiber-chip edge coupling: breaking the critical size limitation
Authors: Yi Xiaolin , Sun Dongyue , Zhao Weike , Li Hanwen , Zhang Long , Shi Yaocheng , Dai Daoxin 
Published: September 2024

Abstract
Efficient coupling between optical fibers and on-chip photonic waveguides has long been a crucial issue for photonic chips used in various applications. Edge couplers (ECs) based on an inverse taper have seen widespread utilization due to their intrinsic broadband operation. However, it still remains a big challenge to realize polarization-insensitive low-loss ECs working at the O-band (1,260–1,360 nm), mainly due to the strong polarization dependence of the mode coupling/conversion and the difficulty to fabricate the taper tip with an ultra-small feature size. In this paper, a high-efficiency and polarization-insensitive O-band EC is proposed and demonstrated with great advantages that is fully compatible with the current 130-nm-node fabrication processes. By introducing an asymmetric bi-level dual-core mode converter, the fundamental mode confined in the thick core is evanescently coupled to that in the thin core, which has an expanded mode size matched well with the fiber and works well for both TE/TM-polarizations. Particularly, no bi-level junction in the propagation direction is introduced between the thick and thin waveguide sections, thereby breaking the critical limitation of ultra-small feature sizes. The calculated coupling loss is 0.44–0.56/0.48–0.61 dB across the O-band, while achieving 1-dB bandwidths exceeding 340/230 nm for the TE/TM-polarization modes. For the fabricated ECs, the peak coupling loss is ∼0.82 dB with a polarization dependent loss of ∼0.31 dB at the O-band when coupled to a fiber with a mode field diameter of 4 μm. It is expected that this coupling scheme promisingly provides a general solution even for other material platforms, e.g., lithium niobate, silicon nitride and so on.
Optimierung der Produktionsplanung und -steuerung für metallische additive Fertigung
Authors: Gaillard Antoine , Rößler Sebastian , Helmholz Johannes , Junglas Sebastian , Boos Wolfgang 
Published: September 2024

Abstract
The high investment costs in machinery for metal additive manufacturing (mAM) favor the emergence of contract manufacturers. This means that bundling several customer orders into one production order is particularly advantageous given the long production times for mAM. However, there is no order processing model that takes the special features of mAM into account. As a result, the requirements of a mAM for order processing are examined using as a reference the Aachen PPS model and process changes are presented.
Automatisierungspotentialmatrix
Authors: Ziegler Christian , Rößler Markus Philipp 
Published: September 2024

Abstract
In the age of the digital revolution and high global competitive pressure, it is essential for companies to identify and strategically exploit automation potentials. The Automation Potential Matrix evaluates the suitability for automation and the expected business benefits. Through this holistic analysis approach, groundbreaking strategic decisions for production can be made in a very short time, while simultaneously avoiding the most significant mistakes in the selection of the form of automation.
Wärmerückgewinnung bei Kompressoren um jeden Preis?
Authors: Gros Dirk 
Published: September 2024

Abstract
The production of compressed air is energy-intensive and involves heat generation. Therefore, connecting compressors to operational heating networks for heat recovery is now state of the art. However, an investing company should be aware that there can also be unnoticed disadvantages for the actual production of compressed air. For energy reasons it is important to avoid operating compressors with a higher final compression temperature than required. For example in order to meet the operating parameters of a heating system. Air-to-air heat recovery can be a cost-effective alternative to save additional heat recovery costs.
Instandhaltung für die Positive Impact Production
Authors: Greimel Lisa , Guhl Jakob , Toth Daniel , Klees Marina , Ansari Fazel 
Published: September 2024

Abstract
The concept of the “Maintenance-Free Factory” describes the transformation of the maintenance management systems to maximise value-added production time, and thereby generating positive impacts for production systems. Yet, concrete tools and methods for implementation have been lacking. This article reveals how the developed tools can be used to determine the initial situation and how companies can be supported with suitable methods to master the path to transform their maintenance to a value-adding partner. Finally, further areas of research and development are explained.
Vorausschauende Instandhaltung und Effizienzbewertung von Niederspannungsmotoren
Authors: Reuter Thomas , Schmidt Jens , Pérez Álvaro Oteros , Grundmann Andreas 
Published: September 2024

Abstract
The consumption of electric drives in industry and manufacturing accounts for almost two-fifths of all electricity in Germany. Electric motors are thus considered to play a key role in energy savings. Energy savings are particularly high in the power range between 0.75 kW and 40 kW, since this is where most operating hours occur each year. At same time, in addition to energy savings, the maintenance of electric drives also plays a decisive role, as sudden failures can result in high costs due to production downtime or repairs. Against this background, a universally applicable condition monitoring system has been developed that allows electrical performance parameters to be analyzed in a simple and compact way in an industrial environment. The aim of this article is to show the added value of electrical power measurement for energy saving and maintenance planning in mechanical glass processing.