bluuebunny/crossref_metadata_2025_split huggingface dataset:
Just Transition as an Evolving Concept in International Climate Law
Authors: Johansson Vilja 
Published: May 2023

Abstract
‘Just transition’ has grown into an increasingly popular concept in climate policy. During the recent decade, it has been included in both international and national climate law frameworks. The concept, however, has not received much attention from legal scholars. Addressing this gap, this article analyses the meaning and legal implications of just transition, specifically within international climate law. Against this backdrop, it shows that, following the Paris Agreement, just transition has evolved into an increasingly important concept in how climate law principles and obligations are interpreted and developed. It further highlights a substantial evolution of just transition from a labour-centred to a more comprehensive concept that helps underline the importance of implementing climate measures in a way that engages and protects affected and vulnerable people and communities.
Long-chain polyphosphates inhibit type I interferon signaling and augment LPS-induced cytokine secretion in human leukocytes
Authors: Pirttiniemi Anniina , Adeshara Krishna , Happonen Natalie , Einarsdottir Elisabet , Katayama Shintaro , Salmenkari Hanne , Hörkkö Sohvi , Kere Juha , Groop Per-Henrik , Lehto Markku 
Published: May 2023

AbstractInorganic polyphosphates are evolutionarily conserved bioactive phosphate polymers found as various chain lengths in all living organisms. In mammals, polyphosphates play a vital role in the regulation of cellular metabolism, coagulation, and inflammation. Long-chain polyphosphates are found along with endotoxins in pathogenic gram-negative bacteria and can participate in bacterial virulence. We aimed to investigate whether exogenously administered polyphosphates modulate human leukocyte function in vitro by treating the cells with 3 different chain lengths of polyphosphates (P14, P100, and P700). The long-chain polyphosphates, P700, had a remarkable capacity to downregulate type I interferon signaling dose dependently in THP1-Dual cells while only a slight elevation could be observed in the NF-κB pathway with the highest dose of P700. P700 treatment decreased lipopolysaccharide-induced IFNβ transcription and secretion, reduced STAT1 phosphorylation, and downregulated subsequent interferon-stimulated gene expression in primary human peripheral blood mononuclear cells. P700 also augmented lipopolysaccharide-induced secretion of IL-1α, IL-1β, IL-4, IL-5, IL-10, and IFNγ. Furthermore, P700 has previously been reported to increase the phosphorylation of several intracellular signaling mediators, such as AKT, mTOR, ERK, p38, GSK3α/β, HSP27, and JNK pathway components, which was supported by our findings. Taken together, these observations demonstrate the extensive modulatory effects P700 has on cytokine signaling and the inhibitory effects specifically targeted to type I interferon signaling in human leukocytes.
Low IL-13Rα1 expression on mast cells tunes them unresponsive to IL-13
Authors: Salomaa Tanja , Kummola Laura , González-Rodríguez Martín Ignacio , Hiihtola Lotta , Järvinen Tero A H , Junttila Ilkka S 
Published: May 2023

Abstract
Cytokine-mediated mast cell regulation enables precise optimization of their own proinflammatory cytokine production. During allergic inflammation, interleukin (IL)-4 regulates mast cell functions, tissue homing, and proliferation, but the direct role of closely related IL-13 for mast cell activation remains unclear. Previous work has shown that mast cells are potent IL-13 producers, but here we show that mouse mast cells do not directly respond to IL-13 by Stat6 activation, as they do not express measurable amount of IL-13 receptor α1 (IL-4Rα1) messenger RNA. Consequently, IL-4 responses are mediated via type I IL-4R (IL-4/IL4Rα/γC), and IL-4–induced Stat6 activation is abolished in γC-deficient mast cells. Type II IL-4R deficiency (IL-13Rα1 knockout) has no effect on IL-4–induced Stat6 activation. In basophils, both IL-4 and IL-13 induce Stat6 activation in wild-type and γC-deficient cells, while in type II IL-4R–deficient basophils, IL-4 signaling is impaired at low ligand concentration. Thus, mast cell and basophil sensitivity to IL-4/IL-13 is different, and in mast cells, lack of IL-13Rα1 expression likely explains their unresponsiveness to IL-13.
Structural and electronic characterization of fluorine-doped La0.5Sr0.5CoO3−δ using electron energy-loss spectroscopy
Authors: Aso Ryotaro , Katsumata Takuya , Nakamura Takashi , Watase Yusuke , Amezawa Koji , Murakami Yasukazu 
Published: May 2023

Abstract
Perovskite oxides, ABO3, are potential catalysts for the oxygen evolution reaction, which is important in the production of hydrogen as a sustainable energy resource. Optimizing the chemical composition of such oxides by substitution or doping with additional elements is an effective approach to improving the activity of such catalysts. Here, we characterized the crystal and electronic structures of fluorine-doped La0.5Sr0.5CoO3−δ particles using scanning transmission electron microscopy (STEM) and electron energy-loss spectroscopy (EELS). High-resolution STEM imaging demonstrated the formation of a disordered surface phase caused by fluorine doping. In addition, spatially resolved EELS data showed that fluorine anions were introduced into the interiors of the particles and that Co ions near the surfaces were slightly reduced by fluorine doping in conjunction with the loss of oxygen ions. Peak fitting of energy-loss near-edge structure data demonstrated an unexpected nanostructure in the vicinity of the surface. An EELS characterization comprising elemental mapping together with an energy-loss near-edge structure analysis indicated that this nanostructure could not be assigned to Co-based materials but rather to the solid electrolyte BaF2. Complementary structural and electronic characterizations using STEM and EELS as demonstrated herein evidently have the potential to play an increasingly important role in elucidating the nanostructures of functional materials.
Survival after introduction of adjuvant treatment in stage III melanoma: a nationwide registry-based study
Authors: Helgadottir Hildur , Ny Lars , Ullenhag Gustav J , Falkenius Johan , Mikiver Rasmus , Olofsson Bagge Roger , Isaksson Karolin 
Published: May 2023

Abstract

Background
Adjuvant treatments with PD-1 and BRAF+MEK inhibitors statistically significantly prolong recurrence-free survival in stage III cutaneous melanoma. Yet, the effect on overall survival is still unclear. Based on recurrence-free survival outcomes, these treatments have been approved and widely implemented. The treatments have considerable side effects and costs, and overall survival effect remains a highly anticipated outcome.

Methods
Clinical and histopathological parameters were obtained from the Swedish Melanoma Registry for patients diagnosed with stage III melanoma between 2016 and 2020. The patients were divided depending on if they were diagnosed before or from July 2018, based on the timepoint when adjuvant treatment was introduced in Sweden. Patients were followed up until the end of 2021. In this cohort study, melanoma-specific and overall survival were calculated using the Kaplan-Meier method and Cox-regression analyses.

Results
There were 1371 patients diagnosed with stage III primary melanoma in Sweden in 2016-2020. The 2-year overall survival rates, comparing the 634 patients in the precohort and the 737 in the postcohort, were 84.3% (95% confidence interval [CI] = 81.4% to 87.3%) and 86.1% (95% CI = 83.4% to 89.0%), respectively, with an adjusted hazard ratio of 0.91 (95% CI = 0.70 to 1.19, P = .51). Further, no statistically significant overall or melanoma-specific survival differences were seen when comparing the precohort and the postcohort in different subgroups for age, sex, or tumor characteristics.

Conclusions
In this nationwide population-based and registry-based study, no survival benefit was detected in patients diagnosed before or after the implementation of adjuvant treatment in stage III melanoma. These findings encourage a careful assessment of the current recommendations on adjuvant treatment.
Shaoyao Gancao Decoction protects against dextran sulfate sodium-induced ulcerative colitis by down-regulating ferroptosis
Authors: Hu Shian , Luo Yue , Yang Xuebing , Zhou Zhe , Zhou Feng , Zhong Lulu , Tan Yang , Pei Gang , Tan Yang 
Published: May 2023

Abstract

Objectives
Shaoyao Gancao Decoction (SGD) is a well-known Chinese herbal prescription used to treat ulcerative colitis (UC). This study was designed to evaluate the effect of SGD in dextran sulfate sodium-induced UC and to reveal the potential mechanism.

Methods
A UC mouse model was established by the administration of dextran sulfate sodium. The mice were given SGD extract intragastrically for 7 days. Histological pathology, inflammatory factors, and ferroptosis regulators were determined in vivo. In addition, ferroptotic Caco-2 cells were prepared to investigate the underlying mechanism of the effects of SGD.

Key findings
The results showed that SGD reduced the disease activity index, the level of inflammatory factors, and histological damage in mice with UC. Moreover, SGD down-regulated the level of ferroptosis in cells in colon tissue, as evidenced by a reduced iron overload, decreased glutathione depletion, and a lower level of malondialdehyde production, compared with the model group. Correspondingly, similar effects of SGD on ferroptosis were observed in Erastin-treated Caco-2 cells. The results of our in vitro reactive oxygen species assays and the changes in mitochondrial structure observed by scanning electron microscopy also supported these results.

Conclusion
Taken together, these findings suggest that SGD protected against UC by down-regulating ferroptosis in colonic tissue.
Poorly differentiated sarcoma of the maxillary sinus: a histopathology dilemma of a rare tumor
Authors: Šimunjak Tena , Šimunjak Boris , Jurlina Martin , Zrno Matea 
Published: May 2023

Abstract
Sarcomas are a rare heterogeneous group of neoplasms of mesenchymal origin. In the redistribution of all head and neck malignancies, sarcomas are represented by only 1%. Herein, we report a case of a 66-year-old patient with right maxillary sinus sarcoma that spread through the ostiomeatal complex, infiltrated the septum, all ethmoid cells, frontal sinus, involved the entire right nasal cavity and penetrated to the nasopharynx. Patient was treated with neoadjuvant chemotherapy, surgery and adjuvant radiotherapy. The histopathology indicated poorly differentiated sarcoma with elements of Ewing’s sarcoma, but also with elements consistent with osteosarcoma. Molecular pathological analysis excluded Ewing's sarcoma. Samples were also sent for review to the other Pathology Clinics. They suggested poorly differentiated high-grade pleomorphic sarcoma with elements of osteosarcoma. The accurate diagnosis of the head and neck sarcoma type can be a histopathology dilemma posing a great challenge in the choice of therapeutic approach, and thus the treatment outcome.
A large dedifferentiated retroperitoneal liposarcoma extended to the testis: a rare case report
Authors: Habonimana Patrice , Niyonkuru Evrard , Nisabwe Simon , Mazti Asmae , Moataz Amine , Dakir Mohamed , Debbagh Adil , Aboutaieb Rachid 
Published: May 2023

Abstract
Liposarcomas are neoplasms of mesodermal origin representing less than 1% of all malignant tumors and 1 to 2% of urogenital lesions. Primary retroperitoneal liposarcomas extending into the inguinal canal are rare. We present the case of a large retroperitoneal liposarcoma invading the left testicle and its spermatic cord. It was diagnosed by imaging as a large mass that compresses surrounding abdominal structures and communicating with the inguinal canal. A surgical intervention consisting of en bloc resection of the tumor and the left testicle with its cord was performed by 2 routes, intercostal and inguinal. Histology showed a dedifferentiated liposarcoma, which is a rare entity with a high rate of malignancy and a poor prognosis. The treatment of choice is wide surgical resection with clear margins; chemotherapy and radiotherapy are less sensitive. The patient did not manifest any particular complaints during the first six months after surgery.
Rheumatoid nodule presenting as an indeterminate soft tissue mass in the sole of the foot
Authors: Patel Ravi , Nand Raghav , Sunderamoorthy Dakshinamurthy 
Published: May 2023

Abstract
A 64-year-old lady with a background of rheumatoid arthritis presented to the foot and ankle clinic with lump underneath the sole of her foot causing significant discomfort. Examination revealed she had a swelling of the first and the second metatarsophalangeal joints. Magnetic resonance imaging revealed abnormal soft tissue thickening between the second and the third metatarsal and a single large encapsulating indeterminate soft tissue mass with a peripheral inflammatory rim. The appearance was suggestive of a malignant sarcoma rather than a rheumatoid nodule or rheumatoid tenosynovitis. The patient was referred to the regional sarcoma unit where the scans were reviewed, and a sarcoma was ruled out. The patient then underwent excision of the indeterminate soft tissue mass. Histology revealed granulomatous infiltration suggestive of a rheumatoid nodule. This has not been described previously in the literature.
Hot on the Trail: Pilgrimage and Crime in Early Modern Spain
Authors: Scott Amanda L 
Published: May 2023

Abstract
Though pilgrims were purportedly sacred travelers, their actual identities and motivations for travel were far from certain. Connotations with criminality and fraud also ran deep. Beginning with a strange case in which an epileptic French priest traveling to Santiago de Compostela was arrested and investigated as an alleged spy, this article considers the ambiguities surrounding pilgrim identity and the difficulty communities had in determining intention and motivation. Drawing upon secular and church records from Navarre, Aragon, and Gipuzkoa, this article examines the methods courts employed to reveal or impose identities, including using complex forensic techniques such as building a blind criminal lineup, associative triangulation of place and person, and relying upon medical and linguistic evaluation. In many cases, these processes of evidence gathering and particularly the idea that suspects could be definitively identified runs contrary to our understanding of the lack of sophistication of early modern criminal procedure and epistemology.
Managing Waste: The Provisioning of Public Latrines and the Disposal of Night Soil in Southern Gold Coast (Ghana), c. 1878–1950
Authors: Amoako-Gyampah Akwasi Kwarteng 
Published: May 2023

Abstract
Although Gold Coast Africans in the pre-colonial period believed that supernatural forces were the final causes of diseases, they were also clearly aware of the health implications of indiscriminate defecation and other environmental pollutants. Two types of latrines existed in the Gold Coast to displace excrement beyond the healthful space of the community. One existed inside the house, which European writers referred to as privy huts. The second type was communal latrines located on the outskirts of the town boundary. Irrespective of the true conditions, European adventurers and later colonial officials viewed the Gold Coast through the prism of the racial politics of the “civilizing mission.” They conceived toileting techniques and practices as well as the management of excrement among Africans as “primitive,” unhygienic, and therefore, anathema to “civilization.” This article examines the provision of latrines and the management and disposal of human excrement in the southern Gold Coast during the colonial period. It demonstrates that despite European claims to superior toileting techniques, latrines provided by the colonial administration before the twentieth century were mostly ad hoc, inadequate, very basic, and inefficient. Similarly, colonial technologies for disposing excrement proved inefficient. Thus, the management of human waste in the Gold Coast posed technocratic barriers to public health and highlighted the limits of colonial measures and technologies.
Clinical Pharmacology of Atovaquone and Proguanil Hydrochloride
Authors: Beerahee Misba 
Published: May 2023

Abstract
Background: Atovaquone and proguanil hydrochloride is a new antimalarial combination that is used for treatment and prophylaxis of malaria.
Methods: The clinical pharmacology of atovaquone and proguanil was reviewed.
Results: Atovaquone is a highly lipophilic compound with low aqueous solubility, the absorption of which is limited by the rate and extent of dissolution. Dietary fat increases the rate and extent of atovaquone absorption, increasing AUC two- to threefold and C fivefold over fasting. Proguanil is rapidly and extensively absorbed regardless of food intake. Atovaquone is highly protein bound (&gt; 99%) but does not displace other highly protein bound drugs in vitro, indicating significant drug interactions arising from displacement are unlikely. Atovaquone is predominantly eliminated unchanged in feces, with negligible excretion in urine. Proguanil is partially metabolized and partially excreted unchanged in urine. Its principal metabolite, cycloguanil, is also excreted in urine. Metabolism of proguanil is mediated in the liver by the cytochrome P450 3A and 2C subfamilies.The elimination half-life of atovaquone is 2 to 3 days in adults and 1 to 2 days in children.The elimination half-lives of proguanil and cycloguanil are 12 to 15 hours in adults and children. Dosage adjustments based on body weight categories in children (Vi dose for 11-20 kg, h dose for &gt;20-30 kg, 3/4 dose for &gt;30-40 kg, and full dose for &gt;40 kg) achieve plasma concentrations that are safe and effective during prophylaxis and treatment of malaria. No dose adjustments for race, proguanil metabolizer status, gender, or elderly patients are needed, or for patients with mild to moderately impaired renal or hepatic function.
Conclusion: The clinical pharmacology of atovaquone and proguanil provides a rationale for the dosing regimens recommended for treatment and prophylaxis of malaria.
Atovaquone and Proguanil Hydrochloride: A Review of Nonclinical Studies
Authors: Pudney Mary , Gutteridge Win , Zeman Anton , Dickins Maurice , Woolley Joseph L. 
Published: May 2023

Abstract
Background: Safe and effective antimalarial drugs are needed for treatment and prophylaxis of malaria. The combination of atovaquone and proguanil hydrochloride is a new antimalarial drug combination that has recently become available in many countries.
Methods: Data were reviewed from nonclinical studies evaluating the microbiology, secondary pharmacology, pharmacokinetics, and toxicology of atovaquone and proguanil hydrochloride.
Results: Atovaquone is highly active against asexual erythrocytic stages of Plasmodium falciparum in vitro (IC60 0.7-6 nM) and in animal models. Proguanil per se has only weak antimalarial activity in vitro (IC50 2.4-19 p.M), and its effectiveness depends on the active metabolite cycloguanil (IC60 0.5-2.5 nM). The combination of atovaquone and proguanil is synergistic in vitro. Both drugs also have activity against gametocytes and pre-erythrocytic (hepatic) stages of malaria parasites. Atovaquone is a ubiquinone antagonist that inhibits mitochondrial electron transport and collapses mitochondrial membrane potential. The proguanil metabolite cycloguanil is a dihydrofolate reductase inhibitor, but the mode of action of proguanil is unknown. In screening evaluations of secondary pharmacology, neither atovaquone nor proguanil had activity that adversely affected gastrointestinal, cardiovascular, or central or autonomic nervous system functions at clinically relevant concentrations. After oral administration, atovaquone exposure is extensive in rats but limited in dogs, while proguanil and cycloguanil exposure is extensive in dogs but limited in rats. In both species, toxicity was related to proguanil exposure, the principal manifestations being salivation, emesis, and loss of body weight. Neither atovaquone nor proguanil was teratogenic or mutagenic. An increased incidence of hepatic adenomas and adenocarcinomas was seen in mice, but not rats, after lifetime exposure to atovaquone, and appears to be related to species-specific differences in hepatic enzymatic activity. No additional toxicity was evident in animals treated with the combination of atovaquone and proguanil hydrochloride compared to those treated with either drug alone.
Conclusion: Nonclinical studies of atovaquone and proguanil hydrochloride supported the clinical development of this combination for treatment and prophylaxis of malaria.
Elevated methemoglobin levels in patients treated with high-dose hydroxocobalamin
Authors: Dyrud Martinus , Niu Jianli , Kohler Lisa 
Published: May 2023

Abstract

Objective
The aim of this study was to assess the impact of hydroxocobalamin (OHCbl) infusion on arterial blood gas and oximetry values in patients with vasoplegic syndrome.

Methods
Blood samples collected from 95 patients receiving OHCbl infusion were assayed using the ABL90 FLEX Plus blood gas analyzer for the concentration of methemoglobin (MetHb), total hemoglobin (tHb), carboxyhemoglobin (COHb), arterial oxygen saturation (SaO2), arterial oxygen partial pressure (PaO2), and arterial carbon dioxide partial pressure (PaCO2). Interference of OHCbl on these variables was evaluated using the measured difference between the preinfusion and postinfusion samples.

Results
Blood MetHb (%) measured after the infusion of OHCbl (5g) were significantly higher than the baseline levels, with a median of 4.8 (IQR, 3.0−6.5) versus 1.0 (IQR, 1.0−1.2) (P &lt; .001). Blood COHb (%) increased from a median of 1.3 (IQR, 1.0−1.8) to 1.7 (IQR, 1.3−2.2) (P &lt; .001) following the OHCbl infusion. No differences were seen in median levels of tHb, PaO2, PaCO2, and SaO2 between pre- and post-OHCbl treatment.

Conclusion
The presence of OHCbl in blood clearly interfered with the oximetry measurements of the hemoglobin component fractions by falsely increasing the levels of MetHb and COHb. Blood levels of MetHb and COHb cannot be reliably determined by the co-oximetry when OHCbl is known or suspected.
The Unbearable Silence of Responsibility
Authors: Lemma Alessandra 
Published: May 2023

Abstract
The responsible therapist is defined as the one who makes a unique ‘psychoanalytic promise’ to the patient: I will allow you to ‘use’ me, within the boundaries of the analytic setting, to serve your best interests in developing a mind of your own. It is suggested that this promise can only be kept if the therapist maintains a horizontal relationship with the patient, that is a structurally similar relationship of equals, and ensures that it does not become a malignant vertical relationship where the therapist abuses the asymmetrical power that is inherent to their role within the analytic relationship. The chapter focuses on the inherent asymmetry in the analytic relationship and its ethical implications. It suggests that the therapist inevitably impacts the analytic process through their needs, desires, anxieties, and defences and engages with the uses and abuses of the concept of countertransference. It proposes that the development of the analytic attitude needs to be articulated in relation to what is termed the ethical chóros. This denotes a principled internal space that regulates practice through supporting self-questioning in relation to our work and the obligations therapists have towards their patients.