bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-temperature ultrafast ChipHPLC-MS
Authors: Weise Chris , Westphal Hannes , Warias Rico , Belder Detlev 
Published: December 2023

AbstractHerein, we present a miniaturized chip-based HPLC approach coupled to electrospray ionization mass spectrometry utilizing temperature to achieve high-speed separations. The approach benefits from the low thermal mass of the microfluidic chip and can form an electrospray from the pre-heated mobile phase. With the help of this technology, isothermal and temperature-programmable operations up to 130°C were pursued to perform reversed-phase separations of pesticides in methanol and ethanol-containing eluents in less than 20 s.
Graphical Abstract
Occupational exposure to vapors, gasses, dusts, and fumes in relation to causes of death during 24 years in Helsinki, Finland
Authors: Jalasto Juuso , Luukkonen Ritva , Lindqvist Ari , Langhammer Arnulf , Kankaanranta Hannu , Backman Helena , Rönmark Eva , Sovijärvi Anssi , Piirilä Päivi , Kauppi Paula 
Published: December 2023

Abstract
Purpose
Environmental particulate matter (PM) exposure has been shown to cause excess all-cause and disease-specific mortality. Our aim was to compare disease-specific mortality by estimated occupational exposure to vapors, gasses, dusts, and fumes (VGDF).

Methods
The data source is the Helsinki part of the population-based FinEsS study on chronic obstructive pulmonary diseases including information on age, education level, main occupation, sex, and tobacco smoking combined with death registry information. We compared estimated VGDF exposure to mortality using adjusted competing-risks regression for disease-specific survival analysis for a 24-year follow-up.

Results
Compared to the no-exposure group, the high occupational VGDF exposure group had sub-hazard ratios (sHR) of 1.7 (95% CI 1.3–2.2) for all cardiovascular-related and sHR 2.1 (1.5–3.9) for just coronary artery-related mortality. It also had sHR 1.7 (1.0–2.8) for Alzheimer’s or vascular dementia-related mortality and sHR 1.7(1.2–2.4) for all respiratory disease-related mortality.

Conclusion
Long-term occupational exposure to VGDF increased the hazard of mortality- to cardiovascular-, respiratory-, and dementia-related causes. This emphasizes the need for minimizing occupational long-term respiratory exposure to dust, gasses, and fumes.
Simulations of the human heat balance during Mount Everest summit attempts in spring and winter
Authors: Błażejczyk Krzysztof , Havenith George , Szymczak Robert K. 
Published: December 2023

AbstractThe majority of research dealing with the impacts of the Himalayan climate on human physiology focuses on low air temperature, high wind speed, and low air pressure and oxygen content, potentially leading to hypothermia and hypoxia. Only a few studies describe the influence of the weather conditions in the Himalayas on the body’s ability to maintain thermal balance. The aim of the present research is to trace the heat exchange between humans and their surroundings during a typical, 6-day summit attempt of Mount Everest in the spring and winter seasons. Additionally, an emergency night outdoors without tent protection is considered. Daily variation of the heat balance components were calculated by the MENEX_HA model using meteorological data collected at automatic weather stations installed during a National Geographic expedition in 2019–2020. The data represent the hourly values of the measured meteorological parameters. The research shows that in spite of extreme environmental conditions in the sub-summit zone of Mount Everest during the spring weather window, it is possible to keep heat equilibrium of the climbers’ body. This can be achieved by the use of appropriate clothing and by regulating activity level. In winter, extreme environmental conditions in the sub-summit zone make it impossible to maintain heat equilibrium and lead to hypothermia. The emergency night in the sub-peak zone leads to gradual cooling of the body which in winter can cause severe hypothermia of the climber’s body. At altitudes < 7000 m, climbers should consider using clothing that allows variation of insulation and active regulation of their fit around the body.
Anchored heat kernel upper bounds on graphs with unbounded geometry and anti-trees
Authors: Keller Matthias , Rose Christian 
Published: December 2023

AbstractWe derive Gaussian heat kernel bounds on graphs with respect to a fixed origin for large times under the assumption of a Sobolev inequality and volume doubling on large balls. The main result is then applied to anti-trees with unbounded vertex degree, yielding Gaussian upper bounds for this class of graphs for the first time. In order to prove this, we show that isoperimetric estimates with respect to intrinsic metrics yield Sobolev inequalities. Finally, we prove that anti-trees are Ahlfors regular and that they satisfy an isoperimetric inequality of a larger dimension.
Biomechanical comparison of headless compression screws versus independent locking screw for intra-articular fractures
Authors: Mandala Meghana , Shaunak Shalin , Kreitmair Paul , Phadnis Joideep , Guryel Enis 
Published: December 2023

Abstract
Purpose
Headless compression screws (HCS) have a variable thread pitch and headless design enabling them to embed below the articular surface and generate compression force for fracture healing without restricting movement. Locking screws have greater variety of dimensions and a threaded pitch mirroring the design of the HCS. The objective of this study is to determine whether locking screws can generate compression force and compare the compressive forces generated by HCS versus locking screws.

Method
A comparison between 3.5-mm HCS versus 3.5-mm locking screws and 2.8-mm HCS versus 2.7-mm locking screws was performed using a synthetic foam bone model (Synbone) and FlexiForce sensors to record the compression forces (N). The mean peak compression force was calculated from a sample of 3 screws for each screw type. Statistical analysis was performed using the one-way ANOVA test and statistical significance was determined to be p =  < 0.05.

Results
The 3.5-mm Synthes and Smith and Nephew locking screws generated similar peak compression forces to the 3.5-mm Acutrak 2 headless compression screws with no statistically significant difference between them. The smaller 2.7-mm Synthes and Smith and Nephew locking screws initially generated similar compressive forces up to 1.5 and 2 revolutions, respectively, but their peak compression force was less compared to the 2.8-mm Micro Acutrak 2 HCS.

Conclusion
Locking screws are able to generate compressive forces and may be a viable alternative to headless compressive screws supporting their use for intra-articular fractures.
Platform trial for off-label oncology drugs using comprehensive genomic profiling under the universal public healthcare system: the BELIEVE trial
Authors: Ishimaru Sae , Shimoi Tatsunori , Sunami Kuniko , Nakajima Miho , Ando Yayoi , Okita Natsuko , Nakamura Kenichi , Shibata Taro , Fujiwara Yasuhiro , Yamamoto Noboru 
Published: December 2023

Abstract
Background
Precision medicine has transformed cancer treatment by focusing on personalized approaches based on genomic abnormalities. However, comprehensive genomic profiling (CGP) and access to targeted therapies are limited in Japan. This study investigates the BELIEVE trial, which aims to improve drug accessibility for patients with actionable genetic abnormalities through off-label drug administration.

Methods
The BELIEVE trial is a platform trial with a single master protocol, conducted under the Clinical Trials Act and the patient-proposed health services (PPHS) scheme. Eligible patients with solid tumors exhibiting actionable alterations were enrolled, and CGP tests covered by national health insurance were employed. Treatment selection, study drugs from collaborating pharmaceutical companies, and treatment schedules adhered to predefined protocols. Primary and secondary endpoints were evaluated, and statistical analysis was conducted based on patient response rates.

Results
The BELIEVE trial offered treatment opportunities for patients with relapse/refractory disease who lacked standard therapies or clinical trial options. This study addresses unmet medical needs and contributes to the establishment of precision medicine systems. Similar trials like NCI-MATCH and TAPUR are being conducted globally. The BELIEVE trial provides a platform for off-label drug administration, collects essential clinical data, and contributes to drug approval applications.

Conclusion
The BELIEVE trial provides hope for patients with actionable genetic abnormalities by facilitating access to targeted therapies through off-label drug administration. It establishes a regulatory framework and promotes collaboration between industry and academia by expanding organ-specific and cross-organ biomarker-based treatments.
Competitive displacement and acaricide resistance of two Rhipicephalus (Boophilus) species collected on commercial farms in South Africa
Authors: van Dalen Ellie M. S. P. , Jansen van Rensburg Candice 
Published: December 2023

AbstractRhipicephalus (Boophilus) microplus, an invasive species to Africa, and the endemic R. (B.) decoloratus are of high economic importance in the cattle industry. Invasion of the alien species in South Africa has mostly been reported for traditional communal grazing areas where it seemed to be rapid and, in some cases, even replaced the native species. The alien species is also assumed to already be resistant to acaricides upon invasion. The presence of R. (B.) microplus on commercial farms was therefore investigated and resistance screening of both species to field concentrations of cypermethrin, amitraz, and chlorfenvinphos was determined by means of the larval immersion test. Results showed that only 3.7% (of 383) tick collections submitted were R. (B.) microplus populations. A further 1.6% (of 383) showed co-existence of the two species. Comparing the level of resistance to the acaricides between the two species indicated a mean phenotypic resistance of 66.2 and 26.5% of R. (B.) decoloratus populations to cypermethrin and amitraz, respectively. This was significantly lower for R. (B.) microplus, with 23.0 and 4.1% of its populations resistant to cypermethrin and amitraz, respectively. Closed commercial farming areas seemed to have a preventative advantage for the invasion of R. (B.) microplus and displacement of R. (B.) decoloratus by R. (B.) microplus. Regular monitoring of these two species may be of high importance to prevent unnecessary financial losses due to insufficient control and increased awareness of the threat of Asiatic babesiosis vectored by R. (B.) microplus.
A point-in-time inventory of chikanda orchids within a wild harvesting wetland area in Mwinilunga, Zambia: implications for conservation
Authors: Tembo Chimwemwe , Phiri Ethel Emmarantia , Syampungani Stephen , Malgas Rhoda Ronette , Maciejewski Kristine , Dube Thembani 
Published: December 2023

AbstractDespite continued wild harvesting, there is limited data that provides estimates on the availability of African edible orchids as a resource, and that identifies the ecological drivers of their dynamics. This study was designed to investigate the relationship between distance from surface water and the diversity, frequency, and population density of chikanda orchids in a harvesting wetland in Mwinilunga, Zambia. Vegetation sampling was conducted using an interrupted belt transect design. Eight 50 m transects were systematically placed and positioned perpendicular (90o) to a stream within three separate orchid communities. Individual plant count was recorded within the 0–10 m, 10–20 m, 20–30 m, 30–40 m, and 40–50 m distance zones. Results showed a statistically significant decrease in the Shannon’s Diversity Index between the distance zones in all three communities (p < 0.05). Mean ranks for orchid taxa frequency and density across the distance zones were significantly different for communities 1 and 2 but not 3 and communities 1 and 3 but not 2, respectively. However, there was a medium to large effect size for distance on frequency and a small to large effect size for distance on density in all three communities. These results suggest that distance from surface water influences the frequency and density of orchid taxa occurring in wetland ecosystems. This implies that for conservation purposes, it may be important to focus on areas close to water when establishing orchid sites for the species investigated in this study.
Developing a diagnostic framework for primary and secondary students’ reasoning difficulties during mathematical problem solving
Authors: Säfström Anna Ida , Lithner Johan , Palm Torulf , Palmberg Björn , Sidenvall Johan , Andersson Catarina , Boström Erika , Granberg Carina 
Published: December 2023

AbstractIt is well-known that a key to promoting students’ mathematics learning is to provide opportunities for problem solving and reasoning, but also that maintaining such opportunities in student–teacher interaction is challenging for teachers. In particular, teachers need support for identifying students’ specific difficulties, in order to select appropriate feedback that supports students’ mathematically founded reasoning without reducing students’ responsibility for solving the task. The aim of this study was to develop a diagnostic framework that is functional for identifying, characterising, and communicating about the difficulties students encounter when trying to solve a problem and needing help from the teacher to continue the construction of mathematically founded reasoning. We describe how we reached this aim by devising iterations of design experiments, including 285 examples of students’ difficulties from grades 1–12, related to 110 tasks, successively increasing the empirical grounding and theoretical refinement of the framework. The resulting framework includes diagnostic questions, definitions, and indicators for each diagnosis and structures the diagnostic process in two simpler steps with guidelines for difficult cases. The framework therefore has the potential to support teachers both in eliciting evidence about students’ reasoning during problem solving and in interpreting this evidence.
How pedagogical content knowledge sharpens prospective teachers’ focus when judging mathematical tasks: an eye-tracking study
Authors: Brunner Kirsten , Obersteiner Andreas , Leuders Timo 
Published: December 2023

AbstractTeachers’ ability to accurately judge difficulties of mathematical tasks is an essential aspect of their diagnostic competencies. Although research has suggested that pedagogical content knowledge (PCK) is positively correlated with the accuracy of diagnostic judgments, experimental studies have not been conducted to investigate how PCK affects perception and interpretation of relevant task characteristics. In an intervention study with a control group, 49 prospective mathematics teachers judged the difficulty of 20 tasks involving functions and graphs while an eye tracker tracked their eye movements. Some of the tasks included characteristics well known to be difficult for students. Participants’ domain-specific PCK of typical student errors was manipulated through a three-hour intervention, during which they learned about the most common student errors in function and graph problems. We found that the process of perception (relative fixation duration on the relevant area in the tasks) was related to judgment accuracy. Pre-post comparisons revealed an effect of the intervention not only on participants’ domain-specific PCK of typical student errors but also on their perception and interpretation processes. This result suggests that domain-specific PCK of typical student errors allowed participants to focus more efficiently on relevant task characteristics when judging mathematical task difficulties. Our study contributes to our understanding of how professional knowledge makes teachers’ judgment processes of mathematical tasks more efficient.
Neuroprotective effect of curcumin against experimental autoimmune encephalomyelitis-induced cognitive and physical impairments in mice: an insight into the role of the AMPK/SIRT1 pathway
Authors: Sadek Mohamed A. , Rabie Mostafa A. , El Sayed Nesrine S. , Sayed Helmy M. , Kandil Esraa A. 
Published: December 2023

AbstractMultiple sclerosis (MS) is an incurable chronic neurodegenerative disease where autoimmunity, oxidative stress, and neuroinflammation collaboration predispose myelin sheath destruction. Interestingly, curcumin, a natural polyphenol, showed a neuroprotective effect in numerous neurodegenerative diseases, including MS. Nevertheless, the influence of curcumin against MS-induced cognitive impairment is still vague. Hence, we induced experimental autoimmune encephalomyelitis (EAE) in mice using spinal cord homogenate (SCH) and complete Freund’s adjuvant, which eventually mimic MS. This study aimed not only to evaluate curcumin efficacy against EAE-induced cognitive and motor dysfunction, but also to explore a novel mechanism of action, by which curcumin exerts its beneficial effects in MS. Curcumin (200 mg/kg/day) efficacy was evaluated by behavioral tests, histopathological examination, and biochemical tests. Concisely, curcumin amended EAE-induced cognitive and motor impairments, as demonstrated by the behavioral tests and histopathological examination of the hippocampus. Interestingly, curcumin activated the adenosine monophosphate (AMP)-activated protein kinase/silent mating type information regulation 2 homolog 1 (AMPK/SIRT1) axis, which triggered cyclic AMP response element-binding protein/brain-derived neurotrophic factor/myelin basic protein (CREB/BDNF/MBP) pathway, hindering demyelination of the corpus callosum. Furthermore, AMPK/SIRT1 activation augmented nuclear factor erythroid 2-related factor 2 (Nrf2), a powerful antioxidant, amending EAE-induced oxidative stress. Additionally, curcumin abolished EAE-induced neuroinflammation by inhibiting Janus kinase 2 /signal transducers and activators of transcription 3 (JAK2/STAT3) axis, by various pathways, including AMPK/SIRT1 activation. JAK2/STAT3 inhibition halts inflammatory cytokines synthesis. In conclusion, curcumin’s neuroprotective effect in EAE is controlled, at least in part, by AMPK/SIRT1 activation, which ultimately minimizes EAE-induced neuronal demyelination, oxidative stress, and neuroinflammation.
Graphical Abstract
Graphical illustration of putative molecular pathways implicated in the management of EAE by curcumin. Curcumin activates AMPK/SIRT1, which in turn activates multiple pathways that hinder neurodegeneration, oxidative stress, and neuroinflammation. Moreover, curcumin conquers the inflammatory pathway JAK2/STAT3/NF-kβ.
Impact of clinicians’ behavior, an educational intervention with mandated blood pressure and the hypotension prediction index software on intraoperative hypotension: a mixed methods study
Authors: de Keijzer Ilonka N. , Vos Jaap Jan , Yates David , Reynolds Caroline , Moore Sally , Lawton Rebecca J. , Scheeren Thomas W.L. , Davies Simon J. 
Published: December 2023

Abstract
Purpose
Intraoperative hypotension (IOH) is associated with adverse outcomes. We therefore explored beliefs regarding IOH and barriers to its treatment. Secondarily, we assessed if an educational intervention and mandated mean arterial pressure (MAP), or the implementation of the Hypotension Prediction Index-software (HPI) were associated with a reduction in IOH.

Methods
Structured interviews (n = 27) and questionnaires (n = 84) were conducted to explore clinicians’ beliefs and barriers to IOH treatment, in addition to usefulness of HPI questionnaires (n = 14). 150 elective major surgical patients who required invasive blood pressure monitoring were included in three cohorts to assess incidence and time-weighted average (TWA) of hypotension (MAP < 65 mmHg). Cohort one received standard care (baseline), the clinicians of cohort two had a training on hypotension and a mandated MAP > 65 mmHg, and patients of the third cohort received protocolized care using the HPI.

Results
Clinicians felt challenged to manage IOH in some patients, yet they reported sufficient knowledge and skills. HPI-software was considered useful and beneficial. No difference was found in incidence of IOH between cohorts. TWA was comparable between baseline and education cohort (0.15 mmHg [0.05–0.41] vs. 0.11 mmHg [0.02–0.37]), but was significantly lower in the HPI cohort (0.04 mmHg [0.00 to 0.11], p < 0.05 compared to both).

Conclusions
Clinicians believed they had sufficient knowledge and skills, which could explain why no difference was found after the educational intervention. In the HPI cohort, IOH was significantly reduced compared to baseline, therefore HPI-software may help prevent IOH.

Trial registration
ISRCTN 17,085,700 on May 9th, 2019.
The Middle Paleolithic of the Balkans: Industrial Variability, Human Biogeography, and Neanderthal Demise
Authors: Dogandžić Tamara 
Published: December 2023

AbstractEurope is characterized by an uneven record of Middle Paleolithic occupations. Specifically, large parts of southeastern Europe display markedly lower site densities and less intensive evidence of human presence than is found elsewhere; this has often resulted in the exclusion of the Balkans from debates related to Pleistocene human adaptation. The discrepancy stems either from the lower population densities of southeastern Europe or an imbalance in research across Europe. Additionally, our understanding of Balkan Middle Paleolithic stone tool industries suffers from the use of Mousterian labels defined when Bordian typology was the chief method of lithic analysis. Industrial facies then defined and still in use include Balkan Charentian, Levallois Mousterian, Micromousterian, Denticulate Mousterian; their relation with the rest of the Eurasian record was and remains unclear. This paper sets aside the issue of scarcity of Pleistocene occupations and tries to address Neanderthal biogeography, and variations in Neanderthal technological behavior and subsistence, based on the available record. It reviews the current Middle Paleolithic record in the Balkans, presents the apparent temporal and spatial trends, and presents the provisional biogeography of hominins, including scenarios for the demise of Neanderthals at or soon after the arrival of modern humans in Europe. The paper ends with a discussion of perspectives for future research arising from this analysis of the available record and proposes some hypotheses regarding the role of the Balkans in the overall context of the occupational history of western Eurasia in the Middle/Late Pleistocene.
Ugi 5-center-4-component reaction of α-amino aldehydes and its application in synthesis of 2-oxopiperazines
Authors: Splandesci Marta , Wróbel Martyna Z. , Madura Izabela D. , Dawidowski Maciej 
Published: December 2023

AbstractA synthetic route leading to densely functionalized 2-oxopiperazines is presented. The strategy employs a 5-center-4-component variant of Ugi multicomponent reaction followed by a deprotection/cyclization sequence. N-Boc-α-amino aldehydes were used for the first time as carbonyl components in a key Ugi 5-center-4-component reaction (U-5C-4CR). It is shown that the presented synthetic route can lead to rigid, heterocyclic scaffolds, as demonstrated by the synthesis of tetrahydro-2H-pyrazino[1,2-a]pyrazine-3,6,9(4H)-trione β-turn mimetic and derivatives of 1,6-dioxooctahydropyrrolo[1,2-a]pyrazine and 3,8-dioxohexahydro-3H-oxazolo[3,4-a]pyrazine.
Graphical abstract